STROKE RISK FACTORS AND THEIR INFLUENCE ON SURVIVAL OF PATIENTS DURING 28 POSTSTROKE DAYS
S. Agaev1, M. Azermacheva1, O. Antuchova2 and V. Alifirova1
1Neurology and Neurosurgery, Siberian state medical university, Tomsk, Russia
2Neurology, FGBU SibFNKTs FMBA Med Center № 2, Seversk, Russia
Abstract
The problem of a stroke is the focus the medical community that is caused high rates of morbidity, mortality and disability of the survived patients (85%). The purpose of research is studying of risk factors (RF) of stroke.
Methods: Prevalence of risk factors and their influence on development of a fatal outcome in 853 patients with a stroke is studied. The outcome of a stroke was estimated for the 28th day from the beginning of a disease. All available sources of information were used: data of interview and examination of the patients, interview to relatives, patient’s records, cards of the outpatient, cards of calls of ambulance and the medical death certificates.
Results: The rate of stroke in men was 45,5%, women – 54,5%. The prevalence of arterial hypertension was 79,4% (women > men). AH of stage I met more often at the survived patients while AH of stage II and III prevailed in group of the dead. The most of patients with AH didn't receive regular hypotensive therapy (72,97%). It was noticed that patients were treated more often sporadically or not treated absolutely in group of the dead. The prevalence of smoking was 30,4% in the studied group (men > women). Prevalence of cardiovascular diseases was 44,2% (women > men). The obliterating atherosclerosis of the lower extremities takes a leading place among vascular diseases, and ischemic heart disease (IHD) - among heart diseases which main form is angina pectoris. IHD is associated more often with a fatal outcome. Prevalence of atrial fibrillation was 16,8% in the studied group (women > men). The myocardial infarction was observed in 13.3% among the examined patients. This indicator was much higher at men, than at women. Diabetes mellitus was revealed at 14,4%, prevalence was much higher at women. When comparing the groups which survived and died it is established that diabetes mellitus is associated with a fatal stroke more often.
Frequency of all RF was higher in the group of the died patients. It is established that one RF is observed at 20,98% examined. The most of patients had a combination of two (33,2%), three (25,2%), four (12,7%), five and more (3,9%) RF.
Conclusion: AH (79,4%), heart diseases (44,2%) and smoking (30,4%) are the most significant RF of a stroke in the studied population. The prevalence of smoking is 7 times higher, of myocardial infarction is twice higher in group of men. AH, heart diseases meet in group of women more often, prevalence of diabetes mellitus is 3 times higher. AH stage II and III, absence or an irregularity of reception the antihypertensive drugs, existence of angina pectoris, atrial fibrillation, diabetes mellitus were the adverse factors influencing a stroke outcome. Results of the analysis of material give the chance to develop reasonable recommendations about prevention and the organization of medical care by the patient with acute cerebrovascular disease.
920
BRAIN-0656
Non-Registered Abstracts
Non-Registered Abstracts
PEDIATRIC STRIATAL WHITE MATTER IS RESISTANT TO ISCHEMIA-INDUCED DAMAGE
J. Ahrendsen1, S. Hickey1, H. Grewal2, R. Traystman3, P. Herson2 and W. Macklin1
1Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, USA
2Anesthesiology, University of Colorado School of Medicine, Aurora, USA
3Pharmacology, University of Colorado School of Medicine, Aurora, USA
Abstract
Introduction: White matter injury following ischemic stroke is a major cause of functional disability. In experimental models of ischemic stroke, in addition to significant neuronal death, oligodendrocytes, the myelin producing cells in the central nervous system, and myelinated axons are also injured. Age-related changes in white matter vulnerability to ischemia have been extensively studied and these studies suggest that both the perinatal and the aged periods are times of increased white matter vulnerability. However, sensitivity of white matter following stroke in the pediatric brain has not been evaluated. Interestingly, the late pediatric period is an important developmental stage, as it is the time of maximal myelination. Due to the high metabolic activity of myelinating oligodendrocytes, we hypothesized that pediatric white matter would be particularly sensitive to ischemia.
Methods: We have developed a middle cerebral artery occlusion (MCAO) mouse model of pediatric stroke in order to understand the cellular responses unique to the juvenile developmental time period. Postnatal day 20–25 or adult (8–12 weeks old) male mice were subjected to 45 minutes of reversible MCAO with an intraluminal filament. Animals were analyzed at 24 hr, 3, 7 and 30 days of recovery.
Results: Neurons in pediatric striatum were vulnerable to ischemic damage, and neuronal death was comparable in pediatric and adult mice following ischemia. By contrast, actively myelinating striatal oligodendrocytes in the pediatric brain were highly resistant to ischemia, whereas adult oligodendrocytes were quite sensitive. As a result, myelin sheaths remained remarkably intact and axons survived well in the injured striatum of pediatric mice, while significant axon damage and tissue loss was observed in adult striatum. In addition to relative resistance of pediatric white matter, we observe very different glial responses in pediatric and adult mice after MCAO, including differences in astrogliosis, fibrosis, NG2-cell reactivity, and vascular integrity.
Conclusions: Together, these results demonstrate that white matter in the pediatric mouse brain is quite resistant to ischemia. Overall, the current study indicates the likelihood that equivalent ischemic insults will result in a tissue environment more conducive to long-term recovery, and potentially less functional deficits in children compared to adults.
921
BRAIN-0103
Non-Registered Abstracts
Non-Registered Abstracts
EFFECT OF DIETARY INCLUSION OF TWO GINGER VARIETIES ON ECTONUCLEOTIDASES AND ACETYLCHOLINESTERASE ACTIVITIES IN SYNAPTOSOMES FROM THE CEREBRAL CORTEX OF HYPERTENSIVE RATS
2Biochemistry, Federal University of Technology Akure P.M.B. 704 Akure 340001 Nigeria, Akure, Nigeria
3Biochemistry, Universidade Federal de Santa Maria Campus Universitário Camobi 97105-900 Santa Maria RS Brazil, Santa Maria, Brazil
Abstract
Ginger and its varieties have been reportedly used in folk medicine for the treatment of several cerebrovascular diseases such as stroke and demetia with little/or no scientific basis for their mechanism of action. Hence, the aim of the present study was to investigate the effects of two ginger varieties on activities of ectonucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes from Nx-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. The animals were divided into seven groups (n = 7): normotensive control rats; hypertensive L-NAME rats; hypertensive control rats treated with Atenolol (10 mg/kg body weight/day); normotensive and hypertensive rats treated with 4% supplementation of red ginger respectively, and normotensive and hypertensive rats treated with 4% supplementation of white ginger respectively. After 14days of pre-treatment with red and white ginger, the animals were induced with hypertension by oral administration of L-NAME 40 mg/kg body weight for 10 days. Then the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results revealed an increase in ATP and adenosine hydrolysis in hypertensive rats when compared with the normotensive control. Also, an increase in AChE activity in the cerebral cortex synaptosomes of L-NAME hypertensive rats was observed. However, dietary supplementation of both ginger varieties was efficient in preventing these alterations in L-NAME hypertensive groups by increasing the levels of ATP and ACh (two important neurotransmitters) in synaptic cleft of cerebral cortex. In conclusion, this study demonstrated that the both ginger rhizomes interfere with the purinergic and cholinergic neurotransmission. Therefore, we can suggest that these activities could provide some possible mechanism of action to justify their use in traditional medicine for the treatment of several cerebrovascular diseases.
922
BRAIN-0407
Non-Registered Abstracts
Non-Registered Abstracts
CREATINE MONOHYDRATE SUPPLEMENTATION FOR 10 WEEKS HAS A POTENTIAL TO IMPROVE LEARNING AND MEMORY IN FEMALE ALBINO MICE FOLLOWING NEONATAL HYPOXIA ISCHEMIA ENCEPHALOPATHY
R. Allah Yar1, F. Iqbal1 and A. Akbar2
1Institute of Pure and Applied Biology, Bahauddin Zakariya University Multan, Multan, Pakistan
2Department of Statistics, Bahauddin Zakariya University Multan, Multan, Pakistan
Abstract
Currently thereare no uniform standard treatments for newborn suffering from cerebralhypoxia-ischemia (HI) and to find new and effective strategies for treating theHI injury remains a key direction for future research. Protective effects of Cragainst ischemic brain injury in animal models remained a subject of interest inseveral studies (Berger et al., 20041; Prass et al., 20072, Beard and Braissant, 20103). Thedetermination of optimal Cr dosage that can be applied following HI injury iscrucial to reduce the brain damage. This is particularly true for humans forwhom no meaningful dose-response data is currently available (Wyss and Schulze, 20024). Therefore, present study was designed to demonstrate theeffect of two different doses of Creatine monohydrate (1 and 3%) on behaviourand brain infarct volume in female albino mice following neonatal hypoxicischemic encephalopathy.
On postnatal day10, animals were subjected to left carotid artery ligation followed by 8%hypoxia for 25 minutes. Following weaning on postnatal day 20, mice weredivided into three treatments on the basis of diet supplementation (Normalrodent diet, 1% and 3% creatine supplemented diet) for 10 week. A battery ofneurological tests (Rota rod, open field and Morris water maze) was used todemonstrate effect of Cr supplementation on neurofunction and infarct sizefollowing HI.
Open field testresults indicated that Cr supplementation had significantly improved locomotoryand exploratory behaviour in subjects. It was observed that Cr treated miceshowed better neuromuscular coordination (rota rod) and improved spatial memory(Morris Water Maze test). A significant affect of creatine supplementation inreducing infarct size was also observed. It was also observed that the micesupplemented with 3% Cr for 10 weeks performed better than those on 1% Cr diet indicatingthat this dose has the potential to improve the neurofunction followingneonatal brain damage.
References
BergerRMiddelanisJVaihingerHMMiesGWilkenBJensenA. Creatine protects the immature brain from hypoxic-ischemic injury. J. Soc. Gynecol. Invest2004; 11: 9–15.PrassKRoylGLindauerUFreyerDMegowDUlrichDStöckler-IpsirogluGWallimannTPrillerJ. Improved reperfusion and neuroprotection by creatine in a mouse model of stroke. J. Cereb. Blood Flow Metabol2007; 27: 452–459.BeardEBraissantO. Synthesis and transport of creatine in the CNS: important for cerebral functions. J. Neurochem2010; 115: 297–313.WyssMSchulzeA. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?Neurosci2002; 112: 243–260.
923
BRAIN-0022
Non-Registered Abstracts
Non-Registered Abstracts
COMPARATIVE STUDY OF RAPID-CYCLING IN BIPOLAR PATIENTS DEPENDENT ON AMPHETAMINE AND INDEPENDENT OF AMPHETAMINE REFERRED TO PSYCHIATRY CLINIC, KERMANSHAH, IRAN, 2012–2014
J. shakeri1, H shakeri2, F arman2 and M shakeri2
1psychiatry department, Behavioral sciences research center, Kermanshah, Iran
2Kermanshah university of medical sciences, Behavioral sciences research center, Kermanshah, Iran
Abstract
Introduction: BMD is a mental disease that is called manic depressive disorder. It is associated with mood changes from low of depression to high of mania. There is same rate in affected male and female. The average age of onset is approximately 21 years. It's called the rapid-cycling if it has at least 4 mood episodes in 12 months.
Aim: This study was designed to evaluate probable causes of rapid-cycling in patients dependent on amphetamine and independent of amphetamine in BMD patients.
Methods: We incorporated a qualitative design that contains one-hundred and ninety four BMD outpatients who fulfilled DSMV-TR criteria. Patients were divided to two groups of dependent on amphetamine and independent of amphetamines. A self-developed and demographic questionnaire was employed. Data was analyzed by SPSS16 software.
Results: In this study 96(49.5%) of patients were dependent on amphetamine and 98 (50.5%) of patients were independent of amphetamine.144 patients (74%) were male and 50 patients (26%) were female. Most prevalent age group were 22 to 40 years old.140 patients (72.16%) patients lived in urban areas and 54 (27.83%) lived in country side. 128 patients (65.97%)were single and 66 patient(34.2%) were married.148 patients (76.28%)had high school education or below and 46 patients(23.71%)had high school diploma or higher education.
The incidence of rapid-cycling in patient's dependent on amphetamine was 23% in contrast to 6% in patients independent of amphetamines, which was statistically significant. (fourfold)
Conclusion: Our study suggests higher incidence of rapid-cycling in amphetamine dependency. We suggest that:
1- Amphetamine dependency should be considered as a possible cause for rapid-cycling in bipolar patients.
2- Treatment of amphetamine dependency should be considered along with treatment of bipolar disorder.
3-It may be possible to prevent rapid-cycling by means of prevention of amphetamine dependency in bipolar patients.
924
BRAIN-0073
Non-Registered Abstracts
Non-Registered Abstracts
SERUM AMYOLID A PLASMA LEVELS AS A PREDICTOR OF INFECTION IN ANEURYSMAL SUBARACHNOID HAEMORRHAGE
L. Azurmendi1, V Degos2, N Tiberti1, N Kapandji2, P Sanchez2, A Sarrafzadeh3, L Puybasset2, N Turck1 and JC Sanchez1
1Human Protein Sciences, Geneva University Hospitals, Geneva, Switzerland
2Department of Anaesthesiology, Pitié-Salpêtrière University, Paris, France
3Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany
Abstract
Introduction: Aneurysmal subarachnoid haemorrhage (aSAH) is associated with high rates of mortality and morbidity[1]. Approximately 40% of the patients die in the first 24 hours after the initial haemorrhage and among the survivors many of them remain hospitalized in the ICU service[2, 3]. Nosocomial infections such as pneumonia, urinary tract infection, bloodstream infection or meningitis are one of the main causes of outcome worsening and death[4]. Until now, no efficient blood biomarker is available for the early detection and prevention of this complication. The aim of this study was to use proteomics strategies to discover biomarkers for infection prediction in aSAH patients.
Material and methods: The plasma proteome of infected (n = 4) and non-infected (n = 4) patients was compared using the 10-plex tandem mass tag (TMT) isobaric labelling quantitative mass spectrometry. Among the differentially expressed proteins the most interesting one was selected for further ELISA verification in 54 infected and 27 no infected patients. The predictive performances were established using Mann-Whitney U tests and ROC curves[5]. The combination of the selected molecule with clinical parameters was established using PanelomiX[6].
Results: At the day of infection, proteomic results gave rise to 17 significantly regulated proteins. Among those, SAA was selected for further studies; its levels were significantly higher in infected patients than in no infected ones (ratio: 15.86). At the admission to the hospital the concentrations of SAA were already significantly higher in patients that will develop an infection during hospitalisation (p = 0.002), reaching a performance of 75.3% (80% SP, 71.8% SE) for a cut-off value of 90.9 µg/mL. Combining SAA with three clinical parameters (white blood cells, WFNS, age) improved its performance to an AUC of 94.4% (100%SP, 83%SE).
Conclusion: Our data suggested that the combination of SAA, an acute phase molecule, with white blood cells, WFNS and age could be an efficient tool for infection determination in aSAH patients. Their prediction capacity could lead to an earlier antibiotherapy and thereby improvement of aSAH patient long-term outcome. In order to evaluate its clinical utility, these results should be validated in a larger multicentric study.
References:
SuarezJITarrRWSelmanWR. Aneurysmal Subarachnoid Hemorrhage. New England Journal of Medicine2006; 354: 387–396.de RooijNKLinnFHvan der PlasJAAlgraARinkelGJ. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry2007; 78: 1365–1372.SchievinkWI. Intracranial Aneurysms. New England Journal of Medicine1997; 336: 28–40.FronteraJAFernandezASchmidtJMClaassenJWartenbergKEBadjatiaNParraAConnollyESMayerSA. Impact of nosocomial infectious complications after subarachnoid hemorrhage. Neurosurgery2008; 62: 80–87.RobinXTurckNHainardATibertiNLisacekFSanchezJCMullerM. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics2011; 12: 1471–2105.RobinXTurckNHainardATibertiNLisacekFSanchezJ-CMüllerM. PanelomiX: A threshold-based algorithm to create panels of biomarkers. Translational Proteomics2013; 1: 57–64.
925
BRAIN-0649
Non-Registered Abstracts
Non-Registered Abstracts
PERSISTENCE OF LEAD NEUROTOXICITY IN ADULT MALE WISTAR RAT: BEHAVIORAL AND HISTOLOGICAL ASPECTS
F.Z. Azzaoui1, H Hami2, A Ahami2, S Boughribil3, S Boulbaroud2, H Bouamama4, M Najimi5 and F Chigr5
1Department of Biology, Faculty of Science Ben M'sik, Casablanca, Morocco
2Department of Biology, Faculty of Science, Kenitra, Morocco
3Department of Biology, Faculty of Sciences and Technology, Mohammedia, Morocco
4Department of Biology, Faculty of Sciences and Technology, Marrakech, Morocco
5Department of Biology, Faculty of Sciences and Technology, Beni Mellal, Morocco
Abstract
Objectives: To investigate the effect of lead persistence on memory and some nervous structures (hippocampus and entorhinal cortex) responsible for the memorization process among adult’s male Wistar rats.
Methods: Two main groups of adult Wistar rats are used; intoxicated rats (n = 12) received 50 mg/L of lead nitrate diluted in tap water, while control ones (n = 12) received tap water only. The intoxication lasted 6 months and the stopping of treatment was for 4 months. Novel Object Recognition memory test and histological study of different cited brain structures are conducted.
Results: The results show that significant decrease is shown in the index of short and long-term recognition memory (p < 0.05) of intoxicated rats, compared to the control ones. Indeed, the hippocampus and the entorhinal cortex of intoxicated rats are too affected even the administration of toxic was stopped; the histological study demonstrate the presence of nuclear pyknosis, cell shrinkage and eosinophilic cytoplasm, in both structures of these groups of rats compared to the control ones.
Conclusion: Lead toxicity remains harmful to nervous system structures and to behavioral performances, even the exposure is stopped.
926
BRAIN-0041
Non-Registered Abstracts
Non-Registered Abstracts
NEUROPROTECTIVE EFFECT OF NEVIRAPINE ON CEREBRAL ISCHEMIC STROKE IN WISTAR RATS
V. Bakshi1 and M Raam1
1Department of Pharmacology and Toxicology, School of Pharmacy Anurag Group of Institutions, Hyderabad, India
Abstract
Objectives: Nevirapine (NVP) is antiretroviral drugs belonging to potent class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) widely used for the treatment human immunodeficiency virus (HIV) infection. The present study was investigated to study the neuroprotective effect of Nevirapine on middle cerebral artery occlusion (MCAO) induced cerebral ischemia in rats and by determining behavioral and biochemical parameters.
Methods: The right middle cerebral artery (MCA) of wistar rats was occluded for 2 h using intraluminal 4-0 monofilament and 22 h reperfusion was allowed. Nevirapine was investigated for its neuroprotective property in cerebral ischemia induced wistar rats at oral dose of 5 and 10 mg kg−1. Nevirapine was administered orally for 14 days prior induction of ischemia. Rats were divided into 5 groups: sham operation, cerebral ischemia-reperfusion untreated (CIRU) group, vehicle treated group (CMC, p.o), Nevirapine low dose group (NVP 5 mg/kg/d), and Nevirapine high dose group (NVP 10 mg/kg/d).
Results: Middle cerebral artery (MCA) occlusion caused significant increase in the glutamate neurotransmitter and also acetylcholinesterase in brain. The neurobehavioral activities were also decreased significantly in MCA occlusion groups. All the alternations induced by ischemia were significantly attenuated by 14 days pretreatment of NVP (5, 10 mg/kg p.o.,) and also exhibited a statistically significant (p < 0.05) depletion of glutamate levels as compared to the negative control group. Additionally Nevirapine also exhibited antioxidant activity by increasing the levels of enzymes like superoxide dismutase, catalase, GSH levels which are statistically significant (p < 0.05) as compared to negative control.
Conclusion: The present study confirms the protective effect of Nevirapine in cerebral ischemia induced by MCAO and improves the behavioral pattern of memory. Pretreatment with nevirapine restored the antioxidant levels and protected the neuronal damage induced by cerebral ischemia.
Effect of Nevirepine on exploratory behavior and y- maze
Values are expressed as mean ± SEM of 6 animals. Superscript letters represent the statistical significance done by ANOVA, followed by Tukey's multiple comparison tests.
p < 0.001 indicates comparision of negative control group with control group
p < 0.001 indicates comparision of low dose group with negative control group
p < 0.001, $$p < 0.01 indicates comparision of high dose with negative control group.
References:
LongaEZWeinsteinPRCarlsonSCumminsR. ‘Reversible middle cerebral artery occlusion without craniectomy in rats,'. Stroke1989; 20: 84–91.EntingRHHoetelmansRM.WLangeJM.A. Antiretroviral drugs and the Central Nervous System. AIDS1998; 12: 1941–1955.Nair, D., Kumar, K.R., Srikumar, B.N., Raju, T.R., Rao, S.B. (2004). Estimation of neurotransmitters n the brain by chromaograhic method. Brain Behav, 134–141.OlufunshoAOlayemiSunday ONwiteJoseph AAdeyemoTitilope A. Investigation of the levels of oxidative stress parameters in HIV and HIV-TB co-infected patients. Journal of infection in developing countries2012; 6: 79–85.
927
BRAIN-0046
Non-Registered Abstracts
Non-Registered Abstracts
ENDOTHELIAL-GLIA ACTIVATION AND NEURODEGENERATION INDUCED BY CYANIDE TOXICITY AND GLOBAL VASCULAR OCCLUSION; A COMPARATIVE STUDY OF TWO RAT MODELS OF ISCHEMIA
W.G. Balogun1, OM Ogundele2, PA.O Adeniyi2, AE Cobham3, AO Ishola2 and A Amin4
1Department of anatomy, University of Ilorin, Ilorin, Nigeria
2Department of anatomy, Afe Babalola university, Ado-Ekiti, Nigeria
3Department of anatomy, University of Calabar, Calabar, Nigeria
4Department of Physiology, university of Ilorin, ilorin, Nigeria
Abstract
Background: The role of the endothelium of cerebral blood vessels in forming an electrical and physical barrier in the brain has long been described as an important filter for the sensitive cells of the central nervous system. The specialised barrier is composed of the endothelial cells of the cerebral arteries, neurons, foot process of ependymal astrocytes, macrophages and microglia cells. In ischemic injury, the alteration of this structural arrangement leads to compromising of the barrier which is further aggravated by oxygen radical production, inflammation and defective metabolism.
Aim: This study compares the changes in the component cells of the blood brain barrier units in global vascular occlusion (GVO) and cyanide toxicity (CN); 2 models of ischemia in rats. This is to differentiate the effect of GVO and cyanide toxicity on endothelial cell proliferation, glia activation, neurodegeneration, neurogenesis and angiogenesis in the cause and progression of ischemic brain injury.
Method: Adult Wistar rats (N = 30) were divided into three groups; VO (n = 12), CN (n = 12) and Control-CO (n = 6). The CN was treated with 30 mg/Kg of KCN; VO was subjected to global vascular occlusion- both for duration of 10 days. The control (CO) was fed on normal rat chow and water for the same duration. At day 10, six animals each were separated into withdrawal groups and renamed (CN-I: n = 6) and VO-I: n = 6). The test groups CN and VO were sacrificed at day 10, while the withdrawal groups CN-I and VO-I were sacrificed at day 20. The brain was excised by dissection and fixed in formolcalcium for antigen retrieval immunohistochemistry (IHC). The following proteins were stained via IHC in the rat brain and blood vessel sections; Neuron (anti-NSE), Astrocytes (anti-GFAP), Endthotelial cells (anti-CD31), Microglia-Monocyte (phagocytic anti-CD45), Neuronal cytoskeleton (anti-NF) and Neurogenesis (anti-NSE, anti-Ki-67). The IHC staining were stereological quantified using image analysis and cell counting techniques.
Result/Discussion: Degenerative changes in CN was rapid compared to VO in the PC, PVZ and the blood vessels. Nitric oxide (NO) over production in cyanide played an important part in the endothelial thickening in the blood vessels in CN (CD31+++) when compared against reduced CD31 expression in CN-I (CD31–). The endothelial activation in CN treatment was linked with a decreased cell proliferation in the neurogenic cells of the PVZ (Ki-67) and monocytes (CD45). The induction of oxidative stress in both VO and CN caused glia activation, although glia was significantly activated in CN than in VO treatment. The GFAP/NSE index shows that glia activation is higher in the PC than PVZ, and higher in cyanide toxicity than vascular occlusion. Cytoskeletal degradation was higher in cyanide treatment (NF-/+) and improved very little in the withdrawal (NF++). In vascular occlusion, the cytoskeletal degeradation was less (NF++) and improved greatly in the withdrawal (NF++++).
928
BRAIN-0869
Non-Registered Abstracts
Non-Registered Abstracts
Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signalling
N. Beaufort1, E Scharrer1, E Kremmer2, V Lux3, M Ehrmann3, R Huber4, H Houlden5, D Werring6, C Haffner1 and M Dichgans7
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians University, Munich, Germany
2Institute of Molecular Immunology, Helmholtz-Zentrum München, Munich, Germany
3Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
4Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
Emeritus Group Structure Research, Max Planck Institute of Biochemistry, Martinsried, Germany
Center for Integrated Protein Science at the Department of Chemistry, Lehrstuhl für Biochemie, Technische Unversität München, Garching, Germany
School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
5Department of Molecular Neuroscience and Neurogenetics Laboratory, University College London, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, United Kingdom
6Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, United Kingdom
7Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians University, Munich, Germany
Munich Cluster for Systems Neurology-SyNergy, Munich, Germany
Abstract
Objectives: CARASIL is an inherited form of cerebral small vessel disease caused by loss-of-function mutations in the high temperature requirement protease HtrA1. HtrA1 is involved in a variety of cellular processes including transforming growth factor β (TGF-β) signalling, and dysregulated TGF-β signaling is considered to promote CARASIL pathogenesis (Hara et al. 2009), but the underlying molecular mechanisms are incompletely understood.
Methods: We analysed the TGF-β pathway in brain tissue and embryonic fibroblasts from HtrA1-deficient mice, as well as in CARASIL patient skin fibroblasts by qPCR, immunoblot and/or immunohistochemisty. We also investigated the proteolytic processing of latent TGF-β binding protein 1 (LTBP-1) by purified, overexpressed or endogenous HtrA1 and characterized the structural and functional consequences of this cleavage using truncated LTBP-1 variants, aminoterminal microsequencing, as well as matrix binding and incorporation assays.
Results: We present evidence for a facilitating role of HtrA1 in TGF-β pathway activation in HtrA1-defficient tissues and cells, and in CARASIL fibroblasts. We identify latent LTBP-1, an extracellular matrix protein and key regulator of TGF-β bioavailability, as a novel HtrA1 target. Cleavage occurs at physiological protease concentrations, is prevented under HtrA1-deficient conditions as well as by CARASIL mutations and disrupts both LTBP-1 binding to fibronectin and its incorporation into the extracellular matrix.
Conclusions: Our results suggest an attenuation of TGF-β signaling caused by a lack of HtrA1-mediated LTBP-1 processing as mechanism underlying CARASIL pathogenesis.
References
HaraKShigaAFukutakeT. Association of HTRA1 Mutations and Familial Ischemic Cerebral Small-Vessel Disease. N Engl J Med2009; 360: 1729–1739.BeaufortNScharrerEKremmerELuxVEhrmannMHuberRHouldenHWerringDHaffnerCDichgansM. Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling. Proc Natl Acad Sci2014; 111(46): 16496–501.
929
BRAIN-0179
Non-Registered Abstracts
Non-Registered Abstracts
IMPLICATION OF C4D IN PROGRESSION OF ISCHEMIC STROKE ON PATIENTS WITH LUPUS ERYTHEMATOSUS
S. Bebitov1, K Mirzaeva1 and G Rakhimbaeva1
1Neurology department, Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
Introduction: Systemic lupus erythematosus (SLE) is one of theuncommon causes of ischemic stroke. According to literature, protein’sconcentrate of complement system (PCS) can be decreased in blood of SLEpatients, but the role of PCS C4d has not been studied completely in ischemicstroke.
Purpose: Aimof our study was to definethe role of PCS C4d inpatients with ischemic stroke, caused by SLE.
Patients and methods: Westudied 42 SLE patients during five years (middle age 45,56 ± 4,23). As an indicator of SLE, all patients, which observedischemic stroke, underwent to magnetic resonance image (MRI). Inaddition, Enzyme – linkedimmunosorbent – Assay(ELISA) wasused for determination of concentrate of PCS C4d in blood.
Results: Concentration of PCS C4d was 0,9 – 0,12 g/l in 54,76% SLE patients with multifocal ischemic stroke on MRI.35,7% of SLE patients had 0,7 – 0,1 g/l PCS C4d concentration with lacunarischemic stroke on MRI. 9,5% SLE patients had 0,4 – 0,6 g/l PCS C4d level withoutischemic stroke signs on MRI.
Conclusions: It should be noted that relatively high concentrationof PCS C4d during a long time might be used as a prognostic marker for ischemicstroke in patients with SLE.
930
BRAIN-0180
Non-Registered Abstracts
Non-Registered Abstracts
AGE AND GENDER FEATURES OF ENCEPHALOPATHY IN LUPUS ERYTHEMATOSUS
S. Bebitov1, K Mirzaeva1 and N Vahobova1
1Neurology department, Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
Objective: We know that encephalopathy is observed as a chroniccomplication in lupus erythematosus (LE). Aim of our study was to establish correlationof encephalopathy in LE with age and gender.
Materials and methods: We studied 38 patients (13 male (M) and 25 female (F)with middle age 31,23 ± 5,32 years) at the neurology and rheumatology departmentof Tashkent Medical Academy. As an indicator of LE, all patients underwent to acutephase reactions (C - reactive protein, gamma globulin and sialic acid). Also duplexscanning of brain vessel carried out for encephalopathy identification.
Results: Acute phase reactions were positive at 72% patients, 88%patients had 0,9–1,1 mm intima mediate complex (IMC). 40% patientsof F had determined cortical dementia, 32% patients were with subcorticaldementia and 28% patients of F with established other local syndromes. In acase of M, these indicators had following numbers: 46,2% - subcorticaldementia, 30,8% - cortical dementia and 23% - other local syndromes.
Conclusion:From theseresults, it can be concluded that, women are more resistant to internal andexternal depressing factors physically and psychologically than men, that iswhy women suffering from erythematosus observed to have more subcorticaldementia while men observed to have more cortical dementia. This study has beencontinuing for confirm accuracy of these results.
931
BRAIN-0181
Non-Registered Abstracts
Non-Registered Abstracts
IMMUNOLOGICAL CHARACTERISTICS AND ANTIGENS OF HLA-SYSTEM IN NEURORHEUMATISM IN UZBEK POPULATION
S Aslanova1, S. Bebitov1 and F Yunusov1
1Neurology department, Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
Introduction: Rheumatic fever(RF) and rheumatic heart disease are still remaining an important public healthproblem. The purpose of the study was determination of immunological parametersand analysis of antigens HLA-class system for RF in a case of neurorheumatism inUzbek population.
Materialsand Methods: We examined 44 patients Uzbek nationality with RF - 26 (59%) women and18 (41%) men at 15–59 years (mean age - 31,9 ± 2,0 years). The control group composed245 healthy individuals of the same nationality. Immunoanalysis performed inperipheral blood of patients.
Resultsand discussion: RF patients showed a significant decrease in the peripheral blood of T-cellpool and immunoregulatory subpopulation (1.4 times), B cells (1.7 times) of thenumber of phagocytic neutrophils, increase of zero lymphocytes and the level ofCircular Immune Complex (3 times). It should be noted that the decrease in T-suppressor was more pronounced than that of T-helper cells, which resulted inincrease in the ratio Th/Ts (3,30 ± 0,15 in the control group and 4,10 ± 0,20- patients).
Occurrence of antigens of HLA-systemwas observed only at loci A and B. Thus, a locus A in 2 times more commonantigen was HLA-A10 (RR = 2,70), in a locus - the greatest risk of developing RFwas for antigen B7 (RR = 2,55), B8 (RR = 2,12), B27 (RR = 5,29), B40 (RR = 2,61).
Conclusion: Neurorheumatismaccompanied by disturbances in the immune system. Genetic markers ofpredisposition to RF in Uzbek people were HLA-A10, B7, B8, B27, B40.
932
BRAIN-0881
Non-Registered Abstracts
Non-Registered Abstracts
INFLUENCE OF ANGIOLIN ON NEUROAPOPTOSIS, CAUSED BY AN IMBALANCE OF REDOX POTENTIAL
I.F. Belenichev1, LI Kucherenko2 and NV Bukhtiyarova1
1Pharmacology and Medical Formulation, Zaporozhye State Medical University, Zaporozhye, Ukraine
2Pharmaceutical Chemistry, Zaporozhye State Medical University, Zaporozhye, Ukraine
Abstract
It is shown that an imbalance of redox potential caused by displacement of thiol-disulfide balance and the accumulation of oxidized forms of thiol-containing molecules under conditions of cerebral pathology can cause neuronal apoptosis. Our studies have shown high neuroprotective activity of Angiolin ((S)-2,6 diaminohexane acid 3-methyl-1,2,4-triazolyl-5-thioacetate) on various models of cerebral pathology and in experiments in vitro. Experiments on cerebral cortex neurons of 14-days-old Wistar rats showed that introduction of oxidized glutathione in 1–5 mM concentration into suspension of neurons results in the activation of caspase-3 and expression of p53. After processing of neurons with ethidium bromide the increase of the number of apoptotically changed cells was noted. The experimental data on dynamics of neuronal apoptosis allow us indirectly connect the action of oxidized glutathione with cascade of reactions of Ras-signaling pathway, as Ras-mediated apoptosis may develop from the level of the protein p53. Pre-processing of neurons with Angiolin (10−5 M) resulted in a significant reduction of the number of apoptotically changed cells. At the same time in the samples with cerebrocurine significant decrease of p53 expression was found. Pronounced antiapoptotic effect of Angiolin takes place indirectly through reduction of p53 protein, which is involved in Ras-mediated apoptosis and causes increase of oxidative stress. Processing of Ras-protein and several other members of this family of proteins of apoptosis intracellular regulation depends on the status of glutathione pool in the cell. Our experiments suggest that Angiolin can increase the ratio reduced/oxidized glutathione, and thus affect the Ras-signaling cascade.
933
BRAIN-0053
Non-Registered Abstracts
Non-Registered Abstracts
PREDICTIVE VALUE OF CIRCULATING VASCULAR ENDOTHELIAL GROWTH FACTOR-1 IN HYPERTENSIVE PATIENTS AFTER ACUTE ISCHEMIC STROKE
A. Berezin1 and O Lisovaya2
1Internal Medicine Department, State Medical University, Zaporozhye, Ukraine
2Cardiology Department, City hospital #6, Zaporozhye, Ukraine
Abstract
Objective: To evaluate value for 6 months survival of vascular endothelial growth factor-1 (VEGF-1) plasma level in hypertensive patients after ischemic stroke.
Design and Methods: 72 mild-to-moderate arterial hypertension patients (47 male, 56–68 aged) within 1–2 weeks after ischemic stroke were enrolled to the scrutiny at baseline and then they were studied prospectively for 6 months period regarding survival rate. All enrolled subjects were similar accordingly clinical status, hemodynamic, Rankin score index, and severity of hypertension. Both VEGF-1 and MMP-9 plasma levels were measured at the study entry and in 6 months after baseline by ELISA. We has been assessed all new cardiovascular events including myocardial infarction (MI), unstable angina (UA), recurrence stroke (RS), TIA, advance heart failure (HF) during study period.
Results: Analysis of obtained outcomes have been shown that all cases (n = 28) of new cardiovascular events identified during first 4 weeks after start of observation are correlated well with VEGF-1 plasma levels (r = −0.58; P < 0.001) measured at baseline. On the other hand, 4-weeks survival rate was 87.0 % and 68.6% respectively for group subjects (P < 0.01) with top and low quartile of VEGF-1 plasma level at baseline. However, lack of tightly interrelationship between cardiovascular outcomes and VEGF-1 (r = 0.2; P = 0.16) in 6 months after study entry. New events associated with RS and TIA incidences independently study period are correlated well with VEGF-1 (r = −0.63; P < 0.05 and r = −0.58; P < 0.02 respectively) only.
Conclusions: We has been proposed that circulating VEGF-1 might have more predicting value in comparison with MMP-9 concentration among hypertensive patients during early ischemic stroke period. The predisposed value of VEGF-1 plasma level toward both RS and TIA incidents during 6 month after stroke could be interesting. The role of circulating VEGF-1 as a prognostic indicator for new cardiovascular events in subjects after ischemic stroke can be discussed.
934
BRAIN-0929
Non-Registered Abstracts
Non-Registered Abstracts
LACTATE TRANSPORT AND RECEPTOR ACTIONS IN RETINA
L. Bergersen1 and M Kolko2
1Oral Biology The Brain and Muscle Energy Group, University of Oslo, Oslo, Norway
2Institute of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Abstract
In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters as well as in the extracellular space, forming a basis for the action of lactate as a volume transmitter of metabolic signals. In addition, a lactate permeable depolarization activated anion channel, recently described in brain astroglia, may cause lactate release in response to neural activity. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose tissue and in brain, and acts also through other down-stream mechanisms to control functions such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina where the retinal ganglion cells die, such as glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Monocarboxylate transporters are previously known to be expressed in retinal cells. We envision that lactate receptors, channnels and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal disease.
935
BRAIN-0686
Non-Registered Abstracts
Non-Registered Abstracts
OPTIMIZING CNS-DELIVERY BY LACTYL STEARATE-COUPLED LIPOSOMES
M. Bhargava1, S Bhargava2 and V Bhargava3
1Pharmacy, ICFAI University Dehradun, Kanpur, India
2Department of Pharmacy, Manav Bharti University, Kanpur, India
3R&D, KRV Hospitals Pvt. Ltd., Kanpur, India
Abstract
Brain drug targeting brings a healthy skepticism to the study of the BBB, which is the most frustrating obstacle for pharmacologists wishing to find treatments for brain disorders. The BBB restricts the brain uptake of many valuable hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic and efficient efflux mechanisms.
Purpose: Meningitis is the inflammation of tissues which covers brain & spinal cord. The drug of choice is rifampicin which is highly lipophilic in nature. Thus lactyl stearate coupled liposomes bearing rifampicin for effective management of meningitis.
Methods: Lactyl stearate was synthesized from stearic acid and lactic acid. Lactyl stearate coupled and uncoupled liposomes bearing rifampicin were prepared by Lipid cast film method using phosphatidyl choline, cholesterol. Formulations were characterized for vesicle shape by Transmission Electron Microscopy (TEM), average vesicle size, drug entrapment efficiency, in-vitro drug release. The in-vivo studies the drug distribution in various organs and blood of albino rats was assessed after I.V. administration of formulations. The quantitative uptake of the formulations by the brain in albino rats was assessed by fluorescent microscopy. On the basis of in-vitro characteristics formulations LIPO-3 and LIPO-3-III-c were taken for in-vivo performance evaluation.
Results & Discussion: The average particle size was found in the range of 2.33 to 1.0 mm for uncoupled and coupled liposomes. The percentage encapsulation efficiency of liposomes was found to be 41% & 34% in uncoupled & coupled liposomes. Brain uptake was increased about 2–3 times in case of uncoupled liposomes as compared to plain drug. Accumulation was increased about 6–8 times with coupled liposomes in comparison to uncoupled liposomes and about 10–12 times higher compared to plain drug solution.
Conclusion: Higher uptake of lactyl stearate coupled liposomes can be explained as, that mono carboxylic acid transporters present on brain endothelial cells and cross the BBB through carrier mediated transport mechanism. Fluorescence study clearly indicates that the preparation is crossing the basal carotid system and accessing to the nervous system. 6-CF was distributed in blood vessels and accumulated in cerebellum and cerebrum. This delivery system not only increased the brain uptake of the drug but it also reduces the administered dose and toxic effect of the drug. Hence it proves great potential in the delivery of the drug into brain for the treatment of the diseases associated with the brain where very limited drug are available for those diseases. Thus, Lactyl stearate coupled liposomes effectively delivers the drug to the brain and has great potential for brain targeting.
936
BRAIN-0687
Non-Registered Abstracts
Non-Registered Abstracts
SURFACE MODIFIED SOLID LIPID NANOPARTICLES FOR THE TARGETED DELIVERY TO BRAIN: MANAGEMENT OF HIV-1 ASSOCIATED DEMENTIA
M. Bhargava1, S Bhargava2 and V Bhargava3
1Pharmacy, ICFAI University Dehradun, Kanpur, India
2Department of Pharmacy, Manav Bharti University, Kanpur, India
3R&D, KRV Hospitals Pvt. Ltd., Kanpur, India
Abstract
Background: HIV-Associated Dementia (HAD) is a significant neurological complication which occurs years after the acute viral sero-conversion reaction responsible for progressive Immuno-suppression and high viral loads. Many patients infected with HIV-1 suffer cognitive impairment ranging from mild to severe HAD which may result from neuronal death in the basal ganglia, cerebral cortex, and hippocampus. With Present available treatment system, there is no satisfactory treatment for HAD available, despite of advancement in the therapeutics.
In this study, nifedipine loaded solid lipid nanoparticles (SLN) were developed for targeting drug into the central nervous system, the site of action of drug to block the apoptosis by HIV-1 virus. This would decrease the process of neurodegeneration and increase the survival time of neuronal cells. Also, this targeted delivery to brain will minimize the systemic effect of nifedipine, avoiding its delivery peripherally.
Method: The uncoated SLN were prepared by Solvent Injection Method & then coated with tween 80 and Lyophylized. Shape & surface morphological studies were done by Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM). The in-vitro release profile of entrapped drug was studied using dialysis membrane. The Ex-vivo studies consisted of DNA fragmentation followed by in-vivo studies on albino rats.
Results: The SEM & TEM images show the smooth & spherical surface of SLN. The in-vitro release profile of drug shows more than 90% of drug release in 48 hrs. DNA fragmentation was determined in presence and in absence of gp120 mimicking agent which shows no DNA fragmentation thus the developed carrier system works properly in releasing the drug and blocking apoptosis in the cortical cells. The fluorescence microscopy shows the qualitative uptake and localization pattern of the coated SLNs in brain.
Conclusion:In-vitro & in-vivo studies results shows more specific delivery of the Nifedipine to the Brain. The DNA Fragmentation & Cell Viability studies shows dementia blocking activity on brain cells. Brain specific delivery of Nifedipine could reduce the dose and potential systemic side effects, thus providing site specific delivery to brain. Thus, CNS delivery of these Nifedipine loaded SLNs via Intra Venous delivery will also open new opportunities for other Anti-Retroviral drug delivery to brain.
937
BRAIN-0822
Non-Registered Abstracts
Non-Registered Abstracts
THE NEUROPROTECTIVE EFFECT OF LEPIDIUM MEYENII (MACA) IN ANIMAL MODEL OF MCAO
K. Taboada-Rosell1, KJ Vera-Lopez2, BS Sousa1, AC Tejeda-Sebastiani1, LB Torres1, LM Quaglio3, BH.S Araújo1, LR Oliveira1, T Maher4, A Pino-Figueroa4 and FR Cabral1
1Brain Institute, Hospital Israelita Albert Einstein, São Paulo, Brazil
2Pharmacology, Universidad Catolica de Santa Maria, Arequipa, Peru
3Phisiology, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil
4Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Science University, Boston, USA
Abstract
Stroke is the third leading cause of death and the major cause of adult disability in the world. Any intervention that could reverse or limit the effects of a stroke would have directly benefits in treatment, rehabilitation and public health. The discovery of new substances for the treatment or prevention of stroke is something extremely promising. In this way, Lepidium meyenii an herbaceous plant belonging to the Brassicaceae family, known as Maca, has been shown to have a great potential for neuroprotection after brain injury. Our study was conducted to evaluate if Maca has potential to be a neuroprotective agent to stand as a new therapeutic drug for stroke. Futhermore, we also evaluated which is the optimal dose and the best therapeutic window for temporary middle cerebral artery occlusion in rats. The experiments were performed on 22 male Wistar rats weighing between 280 and 320 g. The rats were housed in an AAALAC-accredited animal care facility at the Brain Institute of Albert Einstein Hospital. All experimental procedures were approved by the Animal Care and Use Committees of the Albert Einstein Hospital. The animals received twice tail vein injection, the first when anesthetized before surgery (30 min prior to stroke), and the second when the common carotid arteries were reperfused, 1 hour after stroke. The control group received the same treatment as the experimental group, with exception of Maca, which was replaced to aqueous PVP solution. The experimental Maca-group, were treated with different doses of the Maca extract (2,5 mg/kg - n = 6 and 5 mg/kg – n = 8). The effect of Maca on infarction size was evaluated by TTC staining. The brain of the control group did not show any detectable lesion or non-viable tissue damage. However, the brain from the stroke groups showed detectable lesions as white patches in areas that are supplied by the middle cerebral artery. The lesions were present in the lateral striatum and the overlying cortex. Our results show that Maca treatment significantly decreased the lesion (5 mg/kg - P = 0,0002 and 2,5 mg/kg - P = 0,003) in the striatum and cortex of Maca + Stroke groups as compared to control. Whereas the laboratory evidence supports that Maca administration during a time window for produce neuroprotection, extending this treatment at post-stroke period maybe increase its clinical relevance. In Addition, this work provides scientific evidence that Maca may afford neuroprotection for stroke.
938
BRAIN-0889
Non-Registered Abstracts
Non-Registered Abstracts
HEMODYNAMIC CHANGES WITHIN THE DOME OF HUMAN CEREBRAL ANEURYSMS IN RESPONSE TO ARTIFICIALLY-INDUCED INCREASES IN SYSTEMIC BLOOD PRESSURE
H. Hasan1, N Chalouhi2, B Hindman1 and M Todd1
1Neurosurgery, University of Iowa, Iowa city, USA
2Neurosurgery, University of Iowa, Philadelphia, USA
Abstract
Introduction: The formation and rupture of cerebral aneurysms have been associated with hypertension and inflammation. The effect of transient increases in systemic systolic blood pressure (SBP) and its correlation with intra-aneurysmal hemodynamic parameters have not been studied before. The current study is the first to investigate in vivo the effects of transient elevations in systemic SBP on different hemodynamic parameters inside the aneurysm sac and corresponding parent arteries using invasive technology.
Methods: Nine patients with unruptured cerebral aneurysms undergoing coiling were recruited. Dual sensor microwires (0.4 mm diameter) with the capacity to simultaneously measure flow velocity and pressure were used to measure systolic, diastolic and mean pressure inside the aneurysm sac. Additionally, the microwires provided measurement of pressures and peak/mean flow velocities in the parent vessel just outside the aneurysm. The measurements were obtained at baseline and after transient (<10 minutes) incremental increases in systemic SBP up to 25 mm Hg above baseline with a phenylephrine infusion. Systemic hemodynamic parameters (radial arterial catheter) were correlated to intra-aneurysmal and parent arteries parameters.
Results: Eight females and one male (mean age, 54 years; range, 33–74 years) were enrolled. All aneurysms were located in the anterior circulation. The average maximal dose of phenylephrine needed to achieve the required increase in systemic SBP was 0.8 ug/kg/min (range 0.5–1.0). In 8 of 9 patients, acute changes in systemic arterial pressure resulted in simultaneous and at least equal changes in intra-aneurysmal pressures. Three patterns emerged when comparing intra-aneurysmal hemodynamics to changes in systemic hemodynamic parameters: 1) significantly higher increases in aneurysmal compared with systemic pressures; 2) similar variations in aneurysmal and systemic pressures; 3) significantly lower increases in aneurysmal compared with systemic pressures. Peak and mean flow velocities in the parent arteries were decreased after reaching target pressure using phenylephrine infusion without angiographic change in vessel diameter.
Conclusion: These preliminary data suggest that acute increases in systemic pressures are likely to be the underlying mechanism for aneurysm rupture. There may be a subpopulation of aneurysms with exaggerated pressure responses that would be particularly prone to rupture.
939
BRAIN-0393
Non-Registered Abstracts
Non-Registered Abstracts
ACTIVATION OF NMDA RECEPTORS CAUSES DISRUPTION OF MOUSE CEREBRAL ENDOTHELIAL CELLS-CONSTRUCTING TIGHT JUNCTION BARRIERS VIA MEK-/ERK1/2-MEDIATED ACTIVATION OF MMP-2/9
R. Chen1, J Chen1 and Y Chang2
1Graduate Institute of Medical Sciences, Taipei Medical University, Taipei city, Taiwan
2Brain Disease Research Center, Taipei Medical University-Wan Fang Hospital, Taipei city, Taiwan
Abstract
Objectives: The blood-brain barrier (BBB) strictly regulates the brain traversal of immune cells from the bloodstream. Under pathological conditions, neurotransmitter glutamate levels increase dramatically and results in excitotoxic neuronal loss, inflammatory response, and subsequent brain edema. The N-methyl-D-aspartate receptor (NMDAR) is calcium permeable channel gated by glutamate. Roles of NMDARs in the BBB are known little. This study is aimed to evaluate the effects of NMDAR activation on maintenance of the BBB and the possible mechanisms.
Methods: Mouse cerebrovascular endothelial cells (MCECs) were prepared from cerebral microvessels. Expressions of NMDAR mRNA and protein in MCECs were verified. Function of NMDARs was assay using confocal microscopy to analyze intracellular calcium mobilization. Transendothelial electrical resistance (TEER), occluding tight junction, and occludin levels were determined to evaluate the effects of NMDAR activation on the integrity of the MCEC-constructing tight junction barrier. Levels of matrix metalloproteinase (MMP)-2, MMP-9, and phosphorylated and non-phosphorylated (ERK) 1/2 and MEK-1 were analyzed to determine the mechanisms of NMDAR activation-induced disruption of the tight junction barrier.
Results: Protein and RNA analyses revealed the expressions of NMDAR subunits GluN1 and GLUN2B protein or mRNA in MCECs. Confocal microscopic examination further showed GLUN1 could be detected in MCECs and the BBB of mouse brains. Exposure of MCECs to NMDA increased calcium influx in a time-dependent manner. In parallel, treatment with NMDA resulted in significant reductions in the TEER due to disruption of the occludin tight junction and diminishing of occludin synthesis. As to the mechanism, NMDA increased amounts of MMP-2 and MMP-9 in MCECs. Sequentially, exposure to NMDA augmented MEK and ERK1/2 phosphorylations.
Conclusions: This study has shown the functional presence of NMDARs in MCECs, and activation of NMDAR can lead to disruption of MCEC-constructed tight junction barrier via MEK/ERK-induced activation of MMP-2 and MMP-9.
940
BRAIN-0743
Non-Registered Abstracts
Non-Registered Abstracts
BLOOD VOLUME MEASUREMENTS BY DUAL T1 AND T2 MRI ACQUISITIONS WITH SINGLE T2 AGENT IN ACUTE ISCHEMIC RAT BRAIN
JY Suh1, H Jung2, HJ Cho2, YR Kim3 and JK Kim4, G. Cho1
1Magnetic Resonance, Korea Basic Science Institute, Cheongju, Korea
2Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science & Technology, Ulsan, Korea
3Radiology, Martinos Center for Biomedical Imaging Massachusetts General Hospital, Charlestown, USA
4Radiology, Asan Medical Center University of Ulsan college of Medicine, Seoul, Korea
Abstract
Objectives: Blood volume changes duringthe acute phase of brain ischemia are not wellunderstood but presumably linked to other neuronal degenerations. In this study, using theroutinely synthesizable superparamagnetic iron oxide(SPION) as a dual contrast agent, we aimed to quantifyMRI-derived vascular blood volumeparameters in rat ischemicbrain models progressed 24 hrs reperfusion following 1 hr middle cerebral arteryobstruction (MCAO), and compared these parameters with contralesional of the stroke and normal rat brain. We posit that simultaneous acquisitions of both positive and negative contrast-enhancedimages offer complementary information, increasing the certainty and accuracy onthe measurements of blood volumes.
Methods: MRI experiments wereperformed on 3T magnet system (Philips) using rat brains following 24 hrs afterreperfusion submitted to middle cerebral artery occlusion for 60 min (n = 7) andnormal rat brains (n = 5). A kind of 3D T1 MRI signalintensity, ultra-short TE (UTE)sequence was used to quantify absolute cerebral blood volume (aCBV) before and after intravenous administration of superparamagnetic iron oxide nanoparticles (SPION, 6.7 mg/kg).aCBV was calculated using signal changes in brain tissue as compared torelative signal changes in vessel, after creation of subtractionimages (i.e., SIpost_SPION–SIpre_SPION) at 90 flip angle. Additionally, T2- and T2*-weightedimages were acquired before and after SPION injection to obtain relative cerebralvascular blood volume (rCBV, R2*postSPION-R2*preSPION), relative microvascular volume (rMVV, R2postSPION-R2preSPION). Regionsof interests (ROIs) for stroke lesions were drawn by manual contouring on everyslice: the abnormal bright area on the T2 images.
Results: Positive enhancement of signal change in UTE andnegative diminution signal changes in T2(*) images were observed after SPIONinjections due to itsconcurrent T1-T2 effects. From the hemodynamic perspectives, acute phase ofischemic brain seems to be governed by both protective (via flow compensation)and vascular degenerative (disruption of microenvironment) mechanisms. aCBV(measured from UTE) and rCBV (measured from T2*) were increased whereas rMVVmeasured in the ipsilesional subcortex regions were significantly less than thosein the contralesional stroke and normal subcortex areas.
Conclusion: Coupledrelationship between the ischemic tissue damage and increased CBV may suggestthe autoregulatory vasodilation dedicated to therapid normalization of blood oxygen and glucose levels. On the other hand, rMVV decrease in the ipsi-lesion may indicatethe ischemia-induceddefect for the effectiveperfusion reserve that may be used for accurately delineating the true perfusion and neurovascular status.
References
LeeHB. Blood volume in the rat. Nucl. Med1985; 26: 72–76.DennieJ. NMRimaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med1998; 40: 793–799.HuangS. Cerebral blood volume affects blood-brainbarrier integrity in an acute transient stroke model. J Cereb Blood Flow Metab2013 Jun; 33(6): 898–905.
941
BRAIN-0592
Non-Registered Abstracts
Non-Registered Abstracts
THE RELEVANCE OF SOME MEMORY DEFICITS IN A VALPROIC ACID-INDUCED RAT MODEL OF AUTISM
A. Ciobica1, R Lefter2, M Paulet2 and Z Olteanu1
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
Abstract
Background: Autism is a complex disorder characterized by repetitive behavior and impaired social communication. Still, apart from these main manifestations, a significant number of cases display impaired emotional learning and memory functions.
Methods: We tried to better understand the memory functions in an environmentally induced rat animal model of autism, based on the administration of valproic acid (VPA) during gestation (500 mg/kg or saline on day 12.5 of gestation) and examined the resultant progeny on specific memory tests, such as the Y maze task and the 8-arms radial maze.
Results: Our data indicated that animals perinatally exposed to VPA are showing, besides specific social interaction deficiencies, significant behavioral alterations in Y maze task, as expressed in decreased spontaneous alternations percentage, suggesting affected immediate working memory and in the radial arm maze, as expressed to an increased number of both reference and working memory errors.
Conclusions: In conclusion, we showed significant memory deficits in a VPA-induced rat model of autism, demonstrating also the relevance of the memory processes in autism, apart from the social deficiencies.
942
BRAIN-0597
Non-Registered Abstracts
Non-Registered Abstracts
PHYSICAL EXERCISING IS REDUCING ANXIETY, DEPRESSION AND MEMORY DEFICITS ASSOCIATED WITH A MPTP-INDUCED RAT MODEL OF PARKINSON’S DISEASE
A. Ciobica1, M Paulet2, R Lefter2 and D Timofte3
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
3Medicine, “Gr.T. Popa" University, Iasi, Romania
Abstract
Background: It is well known that in Parkinson’s disease (PD), individuals have greater reduction in physical activity levels. Also, inactivity is considered an important factor in accelerating the degenerative process of PD. In addition, PD is known for its cognitive impairments, as well as for depression and anxiety disorders, which may be important causes of morbidity (40% prevalence in PD).
Also, one of the most used animal models of PD is generated by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Methods: We want it to see if induced physical exercising in an MPTP-induced rat model of PD (20 mg/kg i.p.), will result in any changes in memory (as tested in Y maze), anxiety (as tested in elevated-plus-maze) and depression-like behaviour (forced-swim-test), as compared to a non-exercised control group of rats which also received MPTP.
The exercising was performed on an adapted treadmill, for 2 weeks (3 series of 5 minutes/day).
Results: In the group of exercised MPTP group we could observe an increased time spent by the rats in the open arms of the elevated-plus-maze, together with a significant decrease of stretching behaviour and increased head dipping, as compared to non-exercised MPTP group, factors with are suggesting an anxiolytic-like manifestation. In addition, spontaneous alternation in Y maze (index for immediate memory), and swim time (anti-depressive index) in forced swim test were increased in the exercised rats with an MPTP-induced model of PD.
Conclusions: Physical exercising seems to reduce anxiety, depression and memory deficits associated with a MPTP-induced rat model of PD.
943
BRAIN-0600
Non-Registered Abstracts
Non-Registered Abstracts
THE INTERACTION BETWEEN DECREASED SHORT-TERM SPATIAL MEMORY AND INCREASED OXIDATIVE STRESS IN A SCOPOLAMINE-INDUCED RAT MODEL OF ALZHEIMER’S DISEASE
A. Ciobica1, L Hritcu1, R Lefter2, B Stoica3 and D Timofte3
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
3Medicine, “Gr.T. Popa” University, Iasi, Romania
Abstract
Objectives: Scopolamine is a well known muscarinic cholinergic competitive antagonist involved in human and animal memory processes, particularly in the processes of learning acquisition and short-term memory and it has been one of the most used drugs to induce animal models of Alzheimer disease (AD). Also, there is an increased awareness regarding the relevance of the oxidative stress in the progression of AD.
Methods: In this context, we were interested in studying the effects that scopolamine induction of a rat model of AD has on oxidative stress, as expressed by the Total Antioxidant Status (TAS) from the temporal lobe, the most sensitive brain area to the effects of the oxidative stress status.
Results: The cognitive deficits of scopolamine were confirmed in the Y maze task, as expressed through a significant decrease of the spontaneous alternation. Also, our data indicated that the administration of scopolamine has a significant prooxidant effect, which is manifested by a decrease in the TAS of the temporal lobe, as compared to the controls. Moreover, a significant Pearson correlation was observed between the levels of the behavioural tasks and the values of the TAs in the temporal lobe.
Conclusions: In this study we have demonstrated the presence of increased oxidative stress in a rat model of Alzheimer’s disease obtained through the administration of scopolamine. Moreover, there is a significant correlation between the behavioral markers in the Y maze and the levels of TAS, as a result of scopolamine administration.
944
BRAIN-0601
Non-Registered Abstracts
Non-Registered Abstracts
MEMORY DEFICITS IN A KETAMINE-INDUCED RAT MODEL OF SCHIZOPHRENIA
A. Ciobica1, M Paulet2, R Lefter2, L Hritcu1, Z Olteanu1 and D Timofte3
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
3Medicine, “Gr.T. Popa” University, Iasi, Romania
Abstract
Background: Significant cognitive impairment is common in schizophrenia, affecting up to 75% of patients. In this way, it seems that a wide range of cognitive functions are affected, and particularly memory. Moreover, it seems that the cognitive impairment often pre-dates the illness onset.
Also, it is now generally accepted that a subchronic administration of 30 mg/kg ketamine induces reliable changes in behaviour of rat and parameters of dopaminergic, glutamatergic, and serotonergic neurotransmissions, which could resemble to schizophrenia manifestations.
Methods: In this way, in the present experiment, we want it to test if there are any memory deficits in a ketamine-induced rat model of schizophrenia, as tested in the Y maze and radial arm maze tasks. To test this, rats were injected with 30 mg/kg ip ketamine or saline daily for seven consecutive days, while the behavioral experiments were performed 2 weeks after ketamine treatment.
Results: Our data suggested significant memory deficits in this ketamine-induced rat model of schizophrenia in rat, as demonstrated by an increased number of reference memory errors in 8-radial arm maze. Also, the time necessary to finish this test was increased in the ketamine group, as compared to saline. Moreover, the spontaneous alternation percentage was significantly decreased, suggesting deficiencies in the immediate working memory.
Conclusions: Our results presented here suggest that subchronic treatment with subanaesthetic doses of ketamine are inducing significant memory deficits, as tested in the Y maze and radial arm maze tasks.
945
BRAIN-0603
Non-Registered Abstracts
Non-Registered Abstracts
STUDYING PAIN MANIFESTATIONS IN AN MPTP-INDUCED RAT MODEL OF PARKINSON’S DISEASE
A. Ciobica1, R Lefter2, M Paulet2, V Bild3 and D Timofte3
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
3Medicine, “Gr.T. Popa” University, Iasi, Romania
Abstract
Background: Generally, Parkinson's disease (PD) is less widely appreciated as a disease causing pain syndromes, although pain is found in 40–80 % of PD patients, as described by the very few reports in this area of research. Moreover, in some PD patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. Still, pain in PD frequently goes underacknowledged and undertreated. Also, the studies regarding pain perception in the existing animal models of PD are very few.
Methods: We experimentally induced the PD model in rats by injecting subcutaneously one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 20 mg/kg, while the control group received saline. The behavioral testing for pain included the hot-plate task and was performed 7 days after MPTP injection.
Results: In this way, our rat model resulted from the acute treatment with a low dose of MPTP, exhibited an increased sensitivity to pain perception, as demonstrated by the significant decrease in the values of the latency time in hot-plate for rats treated with MPTP, as compared to the controls. The latency time is expressed in seconds and is referring to the reaction time to two different types of behavior: licking the paw and jumping (11.33 ± 2.1 in controls vs. 52.2 % ± 4.1 in MPTP group).
Conclusions: Our data is suggesting, for the first time in our best of knowledge, an increased sensitivity to pain in a MPTP-induced rat model of PD. In this way, further studies in this area of research seem warranted.
946
BRAIN-0607
Non-Registered Abstracts
Non-Registered Abstracts
ONE SINGLE ADMINISTRATION OF MPTP IS ENOUGH TO PRODUCE MEMORY DEFICITS IN A RAT MODEL OF PARKINSON'S DISEASE
A. Ciobica1, R Lefter2, M Paulet2 and D Timofte3
1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania
2SOP HRD/159/1.5/S/133675 Project, Romanian Academy, Iasi, Romania
3Medicine, “Gr.T. Popa” University, Iasi, Romania
Abstract
Background: Besides the well known locomotory aspects, the various neuropsychological investigations of patients with Parkinson's disease (PD) have shown specific cognitive impairments, ranging from minor disturbances in memory to intellectual function or even dementia.
Also, one of the most used animal models of PD in rats in referring to the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Methods: In this way, while most of the administration patterns are including several different intraperitoneally (i.p.) injections of MPTP (e.g. 4 injections X·20 mg/kg, 2 h apart; 1–2 daily injections of MPTP, 20–30 mg/kg, 5 days), here we were interested, for the first time in our best of knowledge, to see if just one acute administration of a single injection of MPTP 20 mg/kg i.p. will result in any cognitive deficits in rats, as studies in the Y maze task. The behavioral testing was performed one week after the MPTP administration, while the control group received saline.
Results: In this way, the administration of single i.p. MPTP dose resulted in a significant decrease of the spontaneous alternation percentage in the Y maze task (77.5 ± 6.2% in controls vs. 52.2 ± 4.1% in MPTP group), suggesting deficits in the immediate working memory. Moreover, these results were not generated by some locomotor deficiencies, considering that there was no significant difference in the number of arm entries between the two groups of rats.
Conclusions: One single i.p. administration of MPTP 20 mg/kg is enough to produce memory deficits in a rat model of PD, as studies in the Y maze task.
947
BRAIN-0586
Non-Registered Abstracts
Non-Registered Abstracts
THE EFFECT OF MUSIC TRAINING PROGRAM ON DEVELOPMENT OF LANGUAGE, COGNITIVE AND MOTOR SKILLS IN CHILDREN USING COCHLEAR IMPLANTS; A RANDOMIZED CONTROL TRIAL
S. Dastgheib1, M Riasi2, M Anvari2, MM Ghasemi2 and M Rajati2
1Neuroscience, Shefa Neuroscience Research Center, Tehran, Iran
2Otolaryngology, Sinus and Surgical Endoscopic Research Center, Mashhad, Iran
Abstract
Objectives: The purpose of this study was to determine whether cochlear-implant (CI) children can gain benefit from music training. Recent studies have shown the role of music training in enhancing language and learning abilities. Our main goals were to provide an opportunity for (CI) children to have access to music training and to determine whether music can improve their language, communication, and cognitive skills rapidly and efficiently.
Study Design: A group of 73 CI children were included in the study and classified into three levels; A, B and C, according to their chronological and hearing age. Children in every level were randomly classified into two groups; music and control. The Newsha Developmental Scale, an integrated test for Persian-speaking CI children, was completed three times by the children’s teachers: before administration of the music program and after the third and sixth month of intervention.
Results: Before the intervention there was no significant difference between the music and control group in any level (P > 0.05). However, after six months of music training program, the mean difference of scores in the music group was significant (P < 0.05) in comparison with the control group in four developmental dimensions: hearing, social contact, cognition, and motor skills.
Conclusions: Although music training program may not significantly improve all language skills in cochlear-implanted children over a short period of time, it can direct deaf children along the path to follow and provide an appropriate platform for CI children to fine tune their language, communication, and cognitive skills.
948
BRAIN-0590
Non-Registered Abstracts
Non-Registered Abstracts
THE EFFECTS OF MOZART’S MUSIC ON INTERICTAL ACTIVITY IN EPILEPTIC PATIENTS: SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE
S. Dastgheib1, P Layegh2, R Sadeghi3, M Foroughipur4, A Shoeibi4 and A Gorji4
1Neuroscience, Shefa Neuroscience Research Center, Tehran, Iran
2Radiology, Mashhad University of Medical Sciences, Mashhad, Iran
3Nuclear Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4Neurology, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Mozart’s music has been shown to have promising effects on nervous system functions. In general, music therapy has been employed as an adjuvant therapy in different neurologic and psychiatric disorders. The impact of Mozart’s music on epilepsy is intriguing. In this study, the effects of Mozart’s work on epilepsy were systematically reviewed. Articles dated up to January 11th, 2013 were obtained from a variety of resources, including Google Scholar, Scopus, MEDLINE, ISI Web of Knowledge and Science Direct. The results of eleven studies addressing Mozart’s music and epilepsy were extracted by two authors who were blinded to each other. Four studies were considered eligible for the meta-analysis. Data analysis indicated that 76.7% of patients listening to Mozart K. 448 showed a significant decrease in epileptic discharges. A noteworthy response to music therapy in patients with a higher intelligence quotient, generalized or central discharges as well as idiopathic epilepsy was demonstrated. Possible mechanisms of effects of music therapy on epilepsy, such as the release of dopamine and modulation of neural network plasticity, were discussed. In conclusion, the effect of Mozart’s music on epilepsy seems to be significant. However, more randomized control studies are needed to determine its clinical efficacy.
949
BRAIN-0882
Non-Registered Abstracts
Non-Registered Abstracts
EVENT-RELATED HIGH FREQUENCY OSCILLATIONS IN THE AGING BRAIN
M. Christov1 and J Dushanova1
1Sensory Neurobiology, Institute of neurobiology Bulgarian Academy of Sciences, Sofia, Bulgaria
Abstract
Background: The brain as a system with gradually decreasing resources by age maximizes its performance by neural networks reorganization for greater efficiency of neuronal oscillations in a given frequency band. Event-related high frequency-band responses, however, have not enough been investigated in the sensory/cognitive mechanisms accompanying aging.
Method: The aged effect on the brain electrical activitywas studied in auditory discrimination task (low–frequency and high–frequency tone) at particular cortical locations in beta (β1:12.5–20; β2:20.5–30 Hz) and gamma frequency bands (γ1:30.5–49; γ2:52–70 Hz) during sensory (post–stimulus interval 0–250 ms) and cognitive processing (250–600 ms).
Results: The beta1 activity less affected by age (only at temporal and parietal area) during sensory processing. The reduced beta1 was more widespread during cognitive processing. This difference increased in fronto–parietal direction more expressed after a high-frequency tone. Beta2 and gamma activity are more pronounced with a progressive age during sensory processing. They reduced by age on cognitive processes. Reducing regional-process specificity with progressing age characterized age-related and tone-dependent beta2 changes during sensory processing. Only the elderly showed higher frontal gamma1 activity during sensory processing. The centres of gamma2 shifted from posterior to anterior brain regions with advancing age.
Conclusion: With increasing age, the frontal brain areas become more sensitive to high-tone discrimination and hand reaction choice. The aged influence was higher on the cognitive processes than on the perceptual ones.
References:
DushanovaJChristovM. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging. Neural Regeneration Research2013; 8: 1390–1399.DushanovaJChristovM. The effect of aging on EEG brain oscillations related to sensory and sensorimotor functions. Advances in Medical Sciences2014; 59: 61–67.DushanovaJPhilipovaDNikolovaG. Beta and gamma frequency-range abnormalities in parkinsonian patients under cognitive sensorimotor task. Journal of the Neurological Sciences2010; 293: 51–58.
950
BRAIN-0051
Non-Registered Abstracts
Non-Registered Abstracts
GABAERGIC/GLUTAMATERGIC IMBALANCE RELATIVE TO NEUROINFLAMMATION AND DYSREGULATED REDOX STATUS IN AUTISM SPECTRUM DISORDERS
A. El-Ansary1 and L Al-Ayadhi1
1Biochemistry, King Saud University, Riyadh, Saudi Arabia
Abstract
Background: Autism spectrum disorder (ASD) is characterized by three core behavioural domains: social deficits, impaired communication, and repetitive behaviours. Glutamatergic/GABAergic imbalance has been found in various preclinical models of ASD. Additionally, autoimmunity immune dysfunction, neuroinflammation , and dysregulated redox status are also considered as etiological mechanisms of this disorder. This study aimed to elucidate the relationship between glutamatergic/ GABAergic imbalance, impaired detoxification, and neuroinflammation as recently-discovered autism-related etiological mechanisms.
Methods: Twenty autistic patients aged 3 to 15 years and 19 age- and gender-matched healthy controls were included in this study. The plasma levels of glutamate, GABA and glutamate/GABA ratio as markers of excitotoxicity, glutathione status , thioredoxin, glutathione-s-transferase as markers of redox status or detoxification, and TNF-α, IL-6, IFN-γ and IFI16 as markers of neuroinflammation were determined in both groups.
Results: Autistic patients exhibited glutamate excitotoxicity based on a much higher glutamate compared to control subjects. Unexpectedly higher GABA and lower glutamate/GABA levels were recorded in autistic patients. While TNF-α and IL-6 were significantly lower, IFN-γ and IFI16 were remarkably higher in the autistic patients than in the control subjects. Poor detoxification ability in autistics was demonstrated and presented as lower GSH/GSSG, higher thioredoxin and less active glutathione-s-transferase.
Conclusion: Multiple regression analysis revealed associations between reduced GABA level, neuroinflammation and glutamate excitotoxicity. This study indicates that autism is a developmental synaptic disorder showing imbalance in GABAergic/ glutamatergic synapses as a consequence of neuroinflammation. Additionally, elevated glutamate was associated with the lower GSH/GSSG and glutathione-s-transferase. This could suggest glutamate signaling as target to treat autism.
951
BRAIN-0052
Non-Registered Abstracts
Non-Registered Abstracts
VITAMIN D STATUS ASSOCIATED WITH NEUROINFLAMMATION AND OXIDATIVE STRESS MARKERS IN AUTISTIC PATIENTS WITH VARYING COGNITIVE AND SOCIAL RESPONSIVENESS SCALES
A. El-Ansary1 and L Al-Ayadhi1
1Biochemistry, King Saud University, Riyadh, Saudi Arabia
Abstract
Objective: Vitamin D deficiency affects 1 billion people worldwide. It has an important role in bone homeostasis, brain development and modulation of the immune system and yet the role of vitamin D deficiency in the etiology of autism is not ascertained. We assessed the levels of 25- hydroxyl vitamin D levels (25(OH) D3) in relation to C-reactive protein (CRP), cytochrome P450 (Cyt P450) and 8 hydroxy deoxyguanine (8-OHdG) in plasma of Saudi autistic patients compared to age and gender matching healthy control participants.
Design and Methods: C reactive protein, Cyt P450and 8-OHdGas biochemical parameters related to inflammation and oxidative stress together with 25(OH) D3, were determined in the plasma of 28 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) or social responsiveness scale (SRS), and compared to 27 age- and gender-matched control samples.
Results: The data indicated that Saudi patients with autism have remarkably lower plasma levels of 25(OH) D3 and Cyt P450 and a significant higher levels of CRP and 8-OHdG compared to age and gender-matched controls. While CRP and 8-OHdG did not correlated with the severity in social and cognitive dysfunction, 25(OH) D3 and Cyt P450 were remarkably associated with the severity of CARS but not SRS.
Conclusions: The relationship between the selected parameters confirms the role of vitamin D deficiency in the etiology of autism and the possibility of using25(OH) D3, Cyt P450, CRP and 8-OHdG as markers of this disorder. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive markers of preclinical presentation of autism and can serve as guide for future therapeutic or protective strategies through vitamin D.
952
BRAIN-0021
Non-Registered Abstracts
Non-Registered Abstracts
DOES CANDESARTAN REDUCE BLOOD- BRAIN BARRIER PERMEABILITY IN TRAUMATIC BRAIN INJURY?
M. eslami1, S khosravi koubanani1, S shafa1, M khaksari1 and Z soltani1
1neuropharmacology research center, Kerman University of Medical Sciences, kerman, Iran
Abstract
Objectives: Traumatic brain injury (TBI) results in complex pathophysiological reactions by secondary cascades including blood–brain barrier dysfunction and edema formation. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT1R) overstimulation links to cerebrovascular remodeling and inflammation leading to neuronal injury. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke. We therefore evaluated effect of candesartan on TBI induced- blood–brain barrier dysfunction.
Methods: The male Albino N-Mary rats were divided to four groups of sham, TBI, vehicle, and candesartan (n = 6 in each group). The diffuse and moderate TBI was induced by Marmarou method. Candesartan (0.3 mg/ kg) or vehicle was administered i.p. The disruption of Blood brain- barrier (BBB) was evaluated by determining brain content of Evans blue, 5 h post- TBI.
Results: The Evans blue dye significantly was higher in TBI and vehicle groups vs. sham group. But that was no different between TBI and vehicle groups. The reduction of TBI- induced BBB disruption was shown with administration of candesartan. The permeability of BBB was significantly different between sham and candesartan groups.
Conclusion: Our data suggest that ARBs may have therapeutic value in treating TBI- induced brain edema by decreasing disruption of BBB.
EARLY REPERFUSION AFTER ISCHEMIC STROKE CONDITIONS BRAIN VASCULAR RESPONSES RELATED TO GLIAL SCAR FORMATION
D. Fernández-López1, J González-Hijón1, I García-Yébenes1, A Moraga1, S Palma1, A García-Culebras1, P Homar1, V Durán1, A Vega1, I Lizasoain1 and MA Moro1
Background: an important fraction (60–65%) of stroke patients undergo early reperfusion spontaneously by dissolution of the thrombus in the absence of thrombolytic therapy, and several studies have agreed that early (<24 h) spontaneous reperfusion results in improved patient outcome. The impact of early reperfusion on the vascular brain component, however, is largely unexplored in both the acute and the chronic phase of stroke. A better understanding of such effects may provide guiding criteria for prediction of patient recovery during the chronic phase based on the presence and timing of early reperfusion and thus help to design more personalized physical and/or pharmacological therapies to promote functional recovery.
Aim: we aimed to explore the effect of early reperfusion on the responses of the brain vascular component (in terms of blood-brain barrier permeability, vascular perfusion, capillary atrophy and stroke-induced angiogenesis) in the ischemic and peri-ischemic brain regions, covering several time points in the acute and chronic phase after experimental stroke.
Methods: distal middle cerebral artery occlusion (MCAO) was performed either permanently (pMCAO) or transiently (60 min occlusion + reperfusion, tMCAO) on C57bl mice. Mice were injected with BrdU in different dose regimes to characterize the time profile of endothelial cell proliferation induced by stroke in both models, and sacrificed at 48 h, 72 h, 5 days, 14 days or 28 days after MCAO. Ten minutes before the sacrifice, mice were administered fluorescently-labeled tomato lectin by tail vein injection in order to monitor vascular perfusion and blood-brain barrier leakage. A different set of mice was used for collection of brain tissue samples for western blot analysis at 14 and 28 days. Vascular density, vessel perfusion, blood-brain barrier permeability, endothelial cell death and proliferation were quantified volumetrically on z-stacks obtained by confocal microscopy, and different parameters related to the glial scar were characterized by microscopy and western blot analysis.
Results: both pMCAO and tMCAO induced a sustained degeneration of the vascular plexus in the ischemic regions, as measured by a decrease in vascular density. Although endothelial cell proliferation in those regions was observed in both models between 24 and 72 hours after MCAO, such acute angiogenic responses to stroke were counteracted by endothelial cell death mostly associated to non-perfused vessels. While the glial scar progressed, a secondary angiogenic response was initiated in the ischemic boundaries, leading to the formation of aberrant and tortuous vessels with a dysfunctional blood-brain barrier. In the mice with early reperfusion this response was exacerbated (p < 0.05, n = 7–8), leading to a higher coverage with blood vessels and enhanced endothelial proliferation. While in both models a clearly defined glial scar was present, the molecular composition of the scar was radically different, suggesting that scar composition may determine long-term stroke-induced angiogenesis.
Conclusions: early reperfusion leads to the formation of a differentiated glial scar after stroke, conditioning endogenous vascular remodeling in the ischemic boundaries. Identifying the molecules involved in astrocyte-endothelial communication would provide novel therapeutic approaches for promotion of vascular remodeling and neural plasticity during the chronic recovery phase after stroke.
EFFECT OF POST-FIXATION ON DIFFUSION TENSOR MRI AND IMMUNOISTOCHEMICAL STAININGS IN THE INFARCTED MOUSE BRAIN
L. Fontana1, P Gelosa2, A Montini1, U Guerrini1, E Tremoli2, M Abbracchio1 and L Sironi1
1Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy
2Unit of Experimental Thrombosis and Imaging in vivo, Centro Cardiologico Monzino, Milano, Italy
Abstract
Objectives: Diffusion Tensor Imaging (DTI) has been used for studying animal models of neurodegenerative diseases, both in-vivo and ex-vivo [1]. Ex-vivo DTI allows higher imaging resolution than in vivo DTI and is free of motion artefacts [2]. A currently unsolved issue is whether in-vivo and ex-vivo DTIs are comparable in terms of detecting white matter alteration under pathological conditions.
Aim of the study was, thus, to identify - in a murine brain ischemia model - a fixation protocol with shorter post-fixation time that allows long scan times and multiple acquisitions, concomitantly preserving tissue from over-fixation.
Methods: Nine adult male C57BL/6J mice, five weeks after permanent middle cerebral artery occlusion (pMCAo), were imaged in-vivo (2D EPI and T2w scans). Mice were subsequently divided in 3 groups and perfused with 10% formalin/PBS. Excised skulls were soaked in 10% formalin for 1 h, 4 h, or 24 h at 4°C, stored in fomblin (a medium that prevents MRI susceptibility artefacts) and finally subjected to at least two ex-vivo acquisitions (3D spin-echo).
Images were processed to extract fractional anisotropy (FA) and diffusivities maps and perform statistical calculations. Quantitative analyses of DTI parameters in two areas of grey matter (somatosensory cortex and striatum) and two of white matter (corpus callosum and main body of corpus callosum) were performed.
After ex-vivo MRI acquisition, the brains were cryopreserved in 30% sucrose and stored at −80°C. Twenty µm cerebral slices were then challenged with specific antigens for astrocytes (GFAP), oligodendrocytes (NG-2, olig2, MBP and GSTpi), macrophages/microglia (Iba1 and CD68), neurons (SMI31) and neuronal precursors cells (DCX).
Results: In healthy hemisphere, diffusivities [Tr(D) = trace, ADC = apparent diffusion coefficient, AD = axial diffusivity, RD = radial diffusivity] are, according to previous data, 25–50% greater in living specimens, as compared with ex-vivo, and substantially homogeneous among different post-fixation times. FA, D‖ (trace-normalised axial diffusivity) and (trace-normalised radial diffusivity) parameters show no significant differences between in-vivo and ex-vivo values. In ischemic hemisphere, % variations of FA, AD, and RD are reduced in ex-vivo specimens in comparison with healthy ones, suggesting a differential effect of fixation on sensitivity of DTI in detecting ischemic damage, without any difference between post-fixation times.
The immunofluorescence analyses for MBP, SMI31, Iba-1, and DCX were not influenced by fixation protocols, whereas for other markers post-fixation time appears to determine the output of immunofluorescence analysis. In our experimental conditions the NG2 antigen was not detectable.
Conclusions: We demonstrated that shorter post-fixation times and storage in fomblin do not affect normalised MRI parameters in healthy tissues, but they still reduce the sensitivity of all DTI parameters in ischemic regions.
The evidence that the immunofluorescence detection of several markers is influenced by fixation protocol should be taken into account when designing ex-vivo MRI analysis coupled with immunofluorescence staining.
References
Jiang Q et al., NeuroImage 32 (2006) 1080–1089.Zhang J et al., MRM 67 (2012) 750–759.
955
BRAIN-0832
Non-Registered Abstracts
Non-Registered Abstracts
EXPERIMENTAL CEREBRAL MALARIA INDUCES CEREBRAL VASCULAR DYSFUNCTION AND COGNITIVE IMPAIRMENT VIA ENDOTHELIN A RECEPTOR SIGNALING
B. Freeman1, YC Martins1, FP Bruno1, DC Spray2 and MS Desruisseaux1
1Pathology, Albert Einstein College of Medicine, Bronx, USA
2Neuroscience, Albert Einstein College of Medicine, Bronx, USA
Abstract
Cerebral malaria (CM) is a serious complication of P. falciparum infection associated with cerebral vasculopathy, high mortality, and adverse neurological sequelae. The vasoactive peptide, endothelin-1 (ET-1), has been shown to mediate blood-brain barrier (BBB) permeability, inflammation, and vascular tone, and may be important in CM pathogenesis. We previously reported that ET-1 was associated with brain microvascular hemorrhage, reduced cerebral blood flow, and mortality in our experimental CM (ECM) model. We predict that these actions were mediated by ET-1 activation of the endothelin A (ETA) receptor. To test the hypothesis that ET-1 is involved in the pathological process of ECM, we investigated ETA receptor mediated signaling in mice infected with P. berghei ANKA (PbA). ETA receptor blockers (ETARB) significantly improved cognitive outcome in mice with ECM. In addition, ETARB enhanced vascular integrity during PbA infection. Intravital microscopy was performed and demonstrated that ETARB treatment prevented cerebral vasoconstriction induced by PbA-infection. BBB permeability, and protein levels of angiopoietin-2 and VCAM-1 were significantly lower in ECM mice treated with an ETARB than in mice treated with saline. Furthermore, ETARB prevented the ECM-induced decrease in angiopoietin-1 in the brains of PbA-infected mice. CM is associated with astrogliosis in both human disease and in experimental models. Our preliminary data indicate that astrogliosis is associated with abnormal protein levels of connexin 43 (Cx43), a gap junction protein critical in gliosis and BBB integrity. ETARB prevented the PbA-induced dysregulation of Cx43. We hypothesized that ET-1 mediated vascular dysfunction in ECM potentially by regulating neuroinflammation and Cx43 expression. In this regard, we observed a significant increase in the activation of JNK in the brains of mice with ECM. JNK, a downstream substrate of ET-1, has been demonstrated to regulate Cx43 expression and function, and is important in CM. Our data indicate that ET-1 may mediate the vascular pathology and neuroinflammation in ECM via regulation of JNK signaling and subsequent Cx43 dysregulation. The ET-1 pathway may thus be a potential therapeutic target as an adjunct therapy in the treatment of human CM.
956
BRAIN-0472
Non-Registered Abstracts
Non-Registered Abstracts
THE POTENTIAL ROLE OF SULFONYLUREA RECEPTOR 1 IN DEVELOPMENT AND THERAPY OF NEONATAL HEMORRHAGIC STROKE
A. Gekalyuk1, OV Semyachkina-Glushkovskaya1, A Shirokov2 and OA Sindeeva1
1Biology, Saratov State University, Saratov, Russia
2Immunochemistry, Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov, Russia
Abstract
Objectives: During the last decade, several studies point to a beneficial effect of glibenclamide to treat stroke[1]. However, the role of Sur1 in neonatal stroke is unclear; the studies in this area are extremely limited. In our previous study, we showed that glibenclamide improves hemorrhagic stroke (HS)-injures of the brain in adult rats but not in newborn rats[2]. To determine potential role of Sur1 in development and therapy of neonatal HS we studied expression of sulfonylurea receptor 1 (Sur1) in the brain tissues of neonates with HS in human and rats as well as we assessed penetration of glibenclamide into brain.
Methods: To study of expression of Sur1 in the brain tissue of neonates with HS in human and rats we used immunofluorescence and immunoblotting. The brain of human neonates extracted in babies (n = 5) who died from HS, the brain newborns who died from severe infection but with the normal brain tissues served as a control group (n = 7). To analyze time-depended changes in expression of Sur1 during HS development we used our model of stress-induced HS (pre-stroke, n = 17; incidence of HS, n = 25). The control group (n = 15) included intact newborn rats. To determine whether glibenclamde penetrate into brain before and after HS in newborn rats, we used glibenclamide injection (BODIPY FL, green fluorescence, 10 µg/kg, iv) in groups: 1) intact rats (the control, n = 10); 2) rats 4 h after stress (pre-stroke, n = 25); 3) rats 24 h after stress (HS, n = 22).
Results: In five died newborns we found subarachnoid hemorrhages, severe edema and hypoxia, congestion of excessive blood in dilated cerebral veins and in vessels of microcirculatory network of pia mater. Sur1 identified in neurons and cerebral capillaries in the HS-injured brain of all studied subjects but not in the control group.
The expression of Sur1 observed in stressed rats 4 h after stress that associated with development of cerebral insufficiency and decreased blood outflow from the brain. The higher expression of Sur1 we found in rats with HS that accompanied by critical changes in the brain such as cerebral hypotention, perivascular edema and severe hypoxia. Sur1 didn’t identify in the brain of healthy rats.
The glibenclamide labeling was present in endothelial cells of cerebral vessels and neurons pre-stroke
but not 24 h after stress.
Conclusion: The upregulation of Sur1 is an important mechanism underlying critical changes on the brain tissues that precede neonatal HS and are associated with HS-injures of brain. These results confirm a beneficial effect of glibenclamide in the treatment of stroke. However, penetration of glibenclamide progressively is reduced in newborn rats with HS and is presented only before HS. Our data suggest that detailed study of effects of glibenclamide for prevention of HS risk in newborns is essential.
References
WooSKKwonMSIvanovA. The sulfonylurea receptor 1 (Sur1)-transient receptor potential melastatin 4 (Trpm4) channel. J. Biol. Chem2013; 288: 3655–3667.The SimardJMGengZWooSKIvanovaS. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. J. Cereb. Blood Flow Metab2009; 29: 317–330.
957
BRAIN-0838
Non-Registered Abstracts
Non-Registered Abstracts
CEREBRAL HEMODYNAMIC RESPONSES TO HYPOCAPNIA AND HYPERCAPNIA: MULTI-WAVELENGTH TIME-RESOLVED STUDIES
A. Gerega1, W Weigl2, D Janusek1, M Kacprzak1 and A Liebert1
1Department for Biophysical Measurements and Imaging, Institute of Biocybernetics and Biomedical Engineering Polish Academy of Science, Warsaw, Poland
2Anaesthesiology and Intensive Care Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
Abstract
Objectives: Recently, near-infrared spectroscopy (NIRS) [1] has a good potential of application at the bedside for assessment of cerebral perfusion and brain oxygenation [2]. We have proposed method of time-resolved diffuse reflectance NIRS with detection of the optical signal at 16 wavelengths. In our study, we investigate the cerebral hemodynamic changes (HbO2 and Hb) during controlled hypo- and hypercapnia. Earlier, the cerebral hemodynamic responses were studied with continuous wave NIRS [3], but extracerebral layers, such as scalp and scull, influence the results of the measurements. Application of the proposed by authors method may allow to improve the depth selectivity of the method.
Methods: A time-resolved NIRS instrument allowing the diffuse reflectance measurements simultaneously at multiple wavelengths on the forehead of a healthy volunteer was used [4]. Measurements of were performed by using of a “supercontinuum” source of light and multichannel time-resolved system based on a time-correlated single-photon counting electronics. The instrument was used to record distributions of times of flight of photons (DTOF’s) at single source–detector separation of 3 cm during normocapnia, hypocapnia (−15 mmHg) and hypercapnia (+15 mmHg). The recorded DTOF’s were analyzed by calculating the statistical moments (the number of diffusely reflected photons, the mean time of flight of photons and the variance of DTOF) for 16 wavelengths from near-infrared region (from 650 to 850 nm with the step of 12.5 nm). The changes of the optical spectra over all detected wavelengths were clearly distinguished due to absorption changes related to changes of hemoglobins concentration during controlled hypocapnia and hypercapnia tests.
Results: In the hypercapnia test, after a 1-minute normocapnia period, a dynamic decrease in the number of photons was observed. However, in the signals of higher-order moments, the changes were observed only at the moment when the CO2 concentration reached its maximum value. This may indicate the effect of autoregulation which under the influence of increased CO2 concentration, leads to weak change in cerebral blood flow (until the ΔCO2 reaches 15 mmHg), while the blood flow in the skin increases.
The polarity of the changes in moments of the DTOF’s in both tests are wavelength-dependent because of the behavior of the hemoglobins during controlled cerebral perfusion changes test. Estimating the concentration changes of HbO2 and Hb was carried out using the algorithm based on estimation of the optical properties from the statistical moments of the measured DTOFs [5] during normocapnia, hypocapnia and hypercapnia. The changes of the HbO2, Hb as well as ΔHbtot are appropriate to its expected behavior.
Conclusions: The method of the multiple wavelength detection may allow for more precise estimation of hemodynamic parameters (ΔHbO2 and ΔHb). The multiwavelength measurement was successfully carried out during hyper- and hypocapnic tests.
The study financed by the Project DOBR/0052/R/ID1/2012/03.
References
Villringer, A., Trends in Neuroscience, 1997.Obrig, H., J Cereb Blood Flow Metab, 2003.Rupp, T., J Cereb Blood Flow Metab, 2014.Gerega, A. in Biomedical Optics and 3-D Imaging. 2012. Miami, USA.Arridge, S.R., Phys Med Biol, 1992.
958
BRAIN-0346
Non-Registered Abstracts
Non-Registered Abstracts
THE ROLE OF TOXIC PROINFLAMMATORY MEDIATOR-CYTOKINES IN CARDIOCEREBRAL SYNDROME
E.I. Giyazitdinova1, AT Azimov1, YA Musaeva1, GS Rakhimbaeva1 and S Musaev2
1Neurology, Tashkent Medical Academy, Tashkent, Uzbekistan
2Neurology, Tashkent Medical Academy, Tashkent, Afghanistan
Abstract
Background and purpose: The aim is our to study the pathological state of microglial cells, which are not recovered to the condition of functional rest and continued to support phlogosis reactions, producing one of toxic proinflammatory mediator-cytokines in cardiocerebral syndrome (CCS) at different times of the acute period of the disease.
Methods: In our observation were 35 patients with CCS, and aged were 34 to 94 years. Spontaneous produce of cytokines in the cerebrospinal fluid from patients determined using monoclonal antibodies.
Results: In patients with CCS on the first day of the disease (7–20 hours after the first symptoms of the disease) showed a significant increase in tumor necrosis factor (TNF-α) to 39.6 ± 6,1 pg/ml, which is 375% of the benchmark. By the third day of illness content TNF-α decreases slightly, amounting to 28,5 ± 3,7 pg/ml (less than the first day of 31.7%). By the tenth day of the disease the content of TNF-α is somewhat reduced, but still has not reached the level of individuals in the control group-19,6 ± 2,5 pg/ml. In 5 patients with CCS the third day of the disease level of TNF-α remained at the same level, and by the tenth day declined slightly.
Conclusion: Thus, the study of cytokines CCS showed the prevalence of the disease in the first day of the inflammatory cytokine TNF-α, which indicates the presence of an inflammatory response in the brain ischemic injury. Dynamic increase in proinflammatory cytokines indicates an increase in neurological deficit and worsening prognosis.
959
BRAIN-0353
Non-Registered Abstracts
Non-Registered Abstracts
ONE OF THE MAIN DIAGNOSTIC CRITERIA OF SMALL VESSELS DISEASE OF THE BRAIN
E.I. Giyazitdinova1, AT Azimov1, S Musaev1, YA Musaeva1 and GS Rakhimbaeva1
1Neurology, Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
Background and purpose: Dilatation of the Virchow-Robin space (VRS) is constantly characterized as markers of cerebrovascular disease, and it is predictor of vascular dementia. The aim of our study was to observe differences in magnetic resonance imaging of dilatation of VRS between subjects with the subcortical ischemic vascular dementia (SIVD), ill-defined cognitively impaired patients and cognitively normal healthy control subjects, as well as the association between the dilatation of VRS and degree of development the subcortical ischemic vascular dementia.
Methods: Thirty five subjects with SIVD, twenty five Ill-defined cognitively impaired patients and twenty healthy volunteers of comparable age and sex were studied. We made out deep white matter , periventricular hyperintensities and the VRS dilatation, as figures of magnetic resonance images. Magnetic resonance imaging of VRS dilatation was compared across groups and examined by VRS dilatation’s location and size.
Results: White matter lesions were more common in patients with SIVD than in those with Ill-defined cognitively impaired or healthy volunteers (P < 0.01). VRS dilatations figures were significantly higher in patients with vascular dementia and SVR were more dilated and prevalenced than in with Ill-defined cognitively impaired patients (P < 0.001). Magnetic resonance images of VRS were normal of healthy volunteers (P < 0.001).
Discussion: Dilatation of the Virchow-Robin Space is one of manifestations in small vessels diseases and can be used as the diagnostic criteria for prognostication ischemic vascular dementia.
960
BRAIN-0370
Non-Registered Abstracts
Non-Registered Abstracts
ELIMINATION OF HYPOKINESIA INDUCED CEREBRAL BLOOD FLOW AND MOTOR COORDINATION DISTURBANCES BY CITICOLINE
T. Grigoryan1, M Balasanyan2 and K Alikhanyan3
1Clinical pharmacology, Yerevan State Medical University, Yerevan, Armenia
2Pharmacology, Yerevan State Medical University, Yerevan, Armenia
3Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia
Abstract
Movement restriction- main problem of modern lifestyle, is one of the important risk factors in a lot of pathologies, including cerebral blood flow (CBF) disorders and stroke. Hypokinesia (HK) leads to development of neurochemical, behavioral and morphological changes of brain, typical for chronic ischemisation [1]. So, the purpose of our study is to investigate the influence of citicoline on CBF disturbances and motor coordination changes under the condition of HK. As a natural endogenous compound, citicoline (cytidine-5´-diphosphocholine; CDP-choline) is an essential intermediate in the synthesis of cell membrane structural phospholipids and its formation is the rate-limiting step in phosphatidylcholine synthesis, which appears beneficial effects in a number of CNS injury models and pathological conditions of the brain.
White inbred male rats weighing 180–220 g were used. For HK rats were kept individually in narrow cages for 15 and 30 days [2]. Motor coordination of rats was investigated in Rota-Rod Treadmill (RRT) test [3]. Animals were anesthetized by intraperitoneal (i/p) injection of nembutal (40 mg/kg). CBF was measured by Laser-Doppler-Flowmeter. During measurement animals were fixed in the stereotaxic apparatus. In the experiments where used animals with high locomotor activity chosen in ‘Open field' test. Hypokinetic animals which didn’t receive any drugs were considered as control group. Experimental group of rats received citicoline at dose of 12,5 mg/kg, i/p twice a day. Paired student's t-test was used to assess to changes of regional CBF and motor coordination parameters. P < 0.05 was selected for statistical significance.
The data obtained have shown that after 15 days of HK citicoline leads to increase of CBF. After the injection of the investigated drug rising of the CBF in 5 minutes have been observed, which reaches its maximum value in the 90th minute (about 28%). The effect of citicoline on CBF after 30-day HK was more prominent: on 90th minute 62% increase of CBF was demonstrated (see table).
CBF changes in % after citicoline administration (12,5 mg/kg, i/p)
Assessment of motor coordination demonstrated citicoline ability to improve it: time spent on the drum by 15-day control group was 29,5 ± 11,5, meanwhile administration of citicoline leaded to the increase of time spending on the drum about 50% (47,5 ± 15,5). HK for 30 days resulted in the significant impairment of motor coordination. Administration of citicoline to the experimental group of rats after 30 days of HK was characterized by increasing of motor coordination more than 5 time compare with 30-day control group.
Thus, our results evident, that citicoline could be used as an effective agent for prevention of cerebral blood flow and motor coordination disturbances in patients with restricted movement activity.
References
Akopyan V.P. et al., Hypokinesia and cerebral blood flow, Med., 1999:p.120–151.Fedorov I.V. et al., Metabolism during hypokinesia, Med., 1982:p.17–25.YangYR. Motor performance improved by exercises in cerebral ischemic rats. J. Mot Behav2012; 44(2): 97–103.
961
BRAIN-0550
Non-Registered Abstracts
Non-Registered Abstracts
FREE RADICAL DEPENDENT NEUROVASCULAR DE-COUPLING IN AN IN VITRO MODEL OF STATUS EPILEPTICUS
L. Hasam Henderson1, I Papageorgiou2, J Swolinsky3, V Muoio4, A Friedman5 and R Kovacs1
1Institute for Neurophysiology, Charite University Medicine Berlin, Berlin, Germany
3Charite, Charite University Medicine Berlin, Berlin, Germany
4Neurosurgery, Hospital Sirio-Libanes, Sao Paulo, Brazil
5Medical Neurosciences, Delhousie University, Nova Scotia, Canada
Free radical dependent neurovascular de-coupling in an in vitro model of status epilepticus
Luisa A. Hasam, Ismini Papageorgiou, Jutta Swolinsky, Valeria Muoio, Alon Friedman, Richard Kovács
Abstract
Objectives: Determine the formation of oxygen centered free radicals during epileptiform activity and their effect on neurovascular coupling and blood brain barrier (BBB) function.
Methods: We used organotypic hippocampal slice cultures (OHSCs) to study the neurovascular coupling and the BBB function during induced epileptiform activity.
In order to assess mitochondrial super oxide production and BBB integrity, OHSCs were stained with MitoSOX/calcein-AM. Peroxide levels were determined by staining dihydrodichlorofluorescein-DA. Fluorescence was monitored in selected vessels in stratum radiatum by using a spinning disk confocal microscope while local field potentials and pO2 recordings were obtained from the CA3 pyramidal layer.
Epileptiform activity was induced by perfusion with modified Mg2+ -free ACSF.
Laminin, NG2 and Hoechst staining was performed to assess pericyte location and alterations of the vascularization following epileptiform activity.
Results: BBB integrity and vascular motility was preserved in OHSCs. Vasoconstriction was elicited by mechanical stimulation of the pericytes, increased intraluminal pressure or by exposure to the thromboxane analogue (U46619). Changes in pericyte length corresponded to changes in vessel diameter.
Pre-constricted vessels dilated following the onset seizure-like events (SLEs) indicating functional neurovascular coupling in OHSCs. However, SLE-associated vasodilatation became smaller during the course of recurrent SLEs.
We observed a terminal vasoconstriction which was associated with the opening of the vessel lumen and with the release of intraluminally accumulated dichlorofluorescein. Remarkably, as revealed by MitoSOX fluorescence, free radical formation was also enhanced in pericytes.
Oxidative metabolism increased during SLEs, as revealed by monitoring tissue pO2. At the same time peroxide formation was enhanced as suggested by oxidation of dihydrodichlorofluorescein. Capillary network disturbances were observed in OHSCs after 12 hours of SLEs cessation.
Conclusion: Overly reduced electron transport chain complexes in presence of high mitochondrial [Ca2+] might facilitate mitochondrial superoxide formation and hydrogen peroxide release.
Free radical formation during epileptiform activity might be sufficient to disturb neurovascular coupling and increase permeability of BBB.
References
Kovács, Richard, Papageorgiou, I., & Heinemann, U.: Slice cultures as a model to study neurovascular coupling and blood brain barrier in vitro. Cardiovascular psychiatry and neurology, vol. 2011, pp. 646958, 2011.Malinska, D., Kulawiak, B., Kudin, A. P., Kovacs, R., Huchzermeyer, C., Kann, O.,…Kunz, W. S.: Complex III-dependent superoxide production of brain mitochondria contributes to seizure-related ROS formation. Biochimica et Biophysica Acta (BBA) - Bioenergetics, vol. 1797, pp. 1163–1170, 2010.Peppiatt, C. M., Howarth, C., Mobbs, P., & Attwell, D.: Bidirectional control of CNS capillary diameter by pericytes. Nature, vol. 443, pp. 700–704, 2006.Yemisci, M., Gursoy-Ozdemir, Y., Vural, A., Can, A., Topalkara, K., & Dalkara, T.: Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nature medicine, vol. 15, pp. 1031–1037, 2009.
962
BRAIN-0211
Non-Registered Abstracts
Non-Registered Abstracts
INFLUENCE OF FISETIN AGAINST HYPERHOMOCYSTEINEMIA INDUCED VASCULAR DEMENTIA AND POSSIBLE ROLE OF FOLIC ACID
B. Hemanth kumar1, A Padmanabha Rao1 and PV Diwan1
1Department of pharmacology, School of Pharmacy Anurag Group of Institutions, HYDERABAD, India
Abstract
Objectives: Fisetin (3, 7, 3′, 4′-tetrahydroxyflavone) belongs to the flavonoid group of polyphenols found in many fruits and vegetables. Folic acid or folate deficiency is well reported in many behavioral disorders and can also lead to hyperhomocystenemia (Hhcy). The main objective of present study is to evaluate therapeutic potential of fisetin perse and in combination with folic acid against hyperhomocystenemia induced vascular dementia.
Methods: Male rats of Wistar type were used in this study. They were treated with homocysteine (Hcy), 0.3–0.6 µmol/g, subcutaneously, twice daily, folic acid , 5 mg/kg, intraperitoneally, fisetin, 15 mg/kg, orally, donepezil, 0.5 mg/kg, intraperitoneally and combination of fisetin with folic acid in the stated doses daily after the second dose of Hcy for one month. Control animals received saline in the same volume as Hcy. Rats were trained on Morris water maze (MWM) and Y-maze and tested for learning and memory tasks using video tracking e-Maze software system. Then, animals were sacrificed by cervical dislocation and blood samples were taken to determine plasma Hcy levels, neutrophill count, serum nitrite and lipid profile (triglycerides, total cholesterol, LDL and HDL). Thoracic aorta was isolated for testing vascular endothelial function and brain tissue was homogenized for determination of acetylcholinesterase activity, glutamate, super oxide dismutase, catalase, reduced glutathione, thiobarbituric acid reactive species. Finally brain histopathology was performed to support the data obtained from behavioural and biochemical estimations.
Results:The results show that the administration of Hcy produced Hhcy and endothelial dysfunction as reflected by significant (P < 0.001) increase in plasma Hcy levels and decrease in serum nitrite concentration. Hcy treated rats have shown impairment in spatial learning and memory tested by MWM and Y-maze. Furthermore, HHcy also induced statistically significant increase (P < 0.001) in brain antioxidant levels, AChE activity, glutamate and serum lipid parameters. fisetin per se and folic acid combination significantly (P < 0.01) attenuated Hcy induced endothelial dysfunction and cognitive impairment. This intervention also significantly (P < 0.001, P < 0.01) lowered the neutrophil count and attenuated all the biomarkers of Hhcy. Furthermore, both fisetin perse and combination with folic acid synergistically attenuated all histological alterations induced by Hhcy.
Conclusions: This study reveals the antioxidant potential of fisetin in Hhcy and vascular dementia and also highlights the possible role of Folic acid in synergizing the effects of fisetin. Further studies are in progress to clarify the mechanisms underlying the synergistic effect of fisetin with folic acid and their relevance as an adjuvant therapy in Hhcy.
References
BazzanoLA. No effect of folic acid supplementation on cardiovascular events, cancer or mortality after 5 years in people at increased cardiovascular risk, although homocysteine levels are reduced. Evid Based Med2011; 16(4): 117–8.MaherPAkaishiTAbeK. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proceedings of the National Academy of Sciences of the United States of America USA2006; 103: 16568–16573.CristianeM. Concurrent folate treatment prevents Na+, K+-ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development. Int. J. Devl Neuroscience2007; 25: 545–552.
963
BRAIN-0042
Non-Registered Abstracts
Non-Registered Abstracts
ACCIDENTAL CHILDREN POISONING WITH METHADONE
N. jafari1, F Farnaghi2 and F Mehregan2
1Neurology, Mofid Hospital, Tehran, Iran
2pediatric, Loghman Hospital, Tehran, Iran
Abstract
Accidental Children Poisoning With Methadone: An Iranian Pediatric Sectional Study
Objective: Toxic poisoning with methadone is common in children in Iran. Our study was carried out due to the changing pattern of methadone poisoning in recent years and increasing methadone toxicity.
Materials & Methods: In this descriptive-sectional study, all of the methadone poisoned children younger than 12 years who were admitted to the Loghman Hakim Hospital in 2012, were assessed. Clinical symptoms and signs, para-clinical findings, and treatment were evaluated.
Results: In this study, 16 boys and 15 girls who had been poisoned by methadone were enrolled. The mean age of patients was 55 months. All patients had been poisoned randomly or due to parent's mistakes. The mean time of symptoms onset after methadone consumption was 1 hour and 30 Min, indicating a relatively long time after onset of symptoms.
Clinical findings were drowsiness (75%), miotic pupil (68 %), vomiting (61%), rapid shallow breathing (57%) and apnea (40%). In paraclinical tests, respiratory acidosis (69%) and leukocytosis (55.2%) were seen. The most important finding was increase in distance of QT in ECG (23.8%). The mean time of treatment with naloxone infusion was 51 hours. Three percent of patients had a return of symptoms after discontinuation of methadone. In patients with apnea, a longer course of treatment was required, and this difference was significant. Also, 17% of patients with apnea had aspiration pneumonia, which was statistically significant.
Conclusion: We suggest long time treatment with naloxone and considering the probability of return of symptoms after discontinuation of methadone.
Keywords: Children; Opium; Methadone; Poisoning.
References
Goldfrank L, Flomenbaum N, Lewin N. Goldfrank's Toxicologic Emergencies. 7th ed. McGraw–Hill 2002; p. 590–607.SchelbleDTPhosgene and phosphine. In: HaddadLMShannonMWWinchesterJ (eds). Clinical Management of Poisoning and Drug Overdose, 3rd ed. Philadelphia: WB Saunders, 2007, pp. 640–7.JenniferCGibsonA. Accidental methadone poisoning in children: A call for Canadian research action. Child Abuse Negl2010; 34(8): 553–4.BinchyJMMolyneuxEManningJ. Accidental ingestion of methadone by children in Merseyside. BMJ1994; 308(6940): 1335–6.ZamaniNSanaei-ZadehHMostafazadehB. Hallmarks of opium poisoning in infants and toddlers. Trop Doct2010; 40(4): 220–2.LoVecchioFPizonARileyBSamiAD'IncognitoC. Onset of symptoms after methadone overdose. Am J Emerg Med2007; 25(1): 57–9.ThanavaroKLThanavaroJL. Methadone-induced torsades de pointes: a twist of fate. Heart Lung2011; 40(5): 448–53.GaalenFACompierEAFogtelooAJ. Sudden hearing loss after a methadone overdose. Eur Arch Otorhinolaryngol2009; 266(5): 773–4.LynchREHackRA. Methadone-induced rigid-chest syndrome after substantial overdose. Pediatrics. 2010126(1): 232–4.SidloJValuchJOckoPBauerováJ. Fatal methadone intoxication in a 11-month-old male infant. Soud Lek2009; 54(2): 23–5.
964
BRAIN-0712
Non-Registered Abstracts
Non-Registered Abstracts
MRI-BASED, PREDICTABLE OPENING OF BLOOD BRAIN BARRIER USING HYPEROSMOLAR AGENT FOR PRECISE INTRA-ARTERIAL DRUG DELIVERY
M. Janowski1, M Pearl1 and P Walczak1
1Radiology, Johns Hopkins University, Baltimore, USA
Abstract
Purpose: Hyperosmolar opening of BBB for effective delivery of drugs to the central nervous system has been attempted for years, but variability of results prohibited wide clinical acceptance. Here, we used MRI guidance to overcome that limitation and to target desired brain area in a highly predictable fashion.
Methods: After catheter placement in cerebral arteries under x-ray guidance, eight 4-kg New Zealand white rabbits under general anesthesia were transported to a 3T MRI (Magnetom Trio, Siemens) and underwent baseline T2 (TR/TE 1500/105) and T1 (TR/TE 300/9.1) weighted images of the brain. The horizontal plane best displayed the brainstem in its entirety and was chosen as the working view for dynamic susceptibility contrast (DSC) enhanced trans-catheter perfusion. IA Feraheme (dissolved in saline at 1:100; 0.3 mgFe/ml) was infused between 0.001 ml/sec to 0.1 ml/sec for 30 seconds to assess the trans-catheter parenchymal perfusion territory at specific speeds. Real-time GE-EPI images (TE = 36 ms, TR = 3000 ms, FOV = 1080, matrix = 128, and temporal resolution = 3 s) were obtained for DSC. Immediately after the Feraheme injection, 25% IA mannitol was administered at the optimal rate previously determined by the Feraheme injection to produce targeted BBBO. The duration of the mannitol infusion was determined by the infusion speed. Five minutes after IA mannitol, 1.5 ml of gadolinium (Magnevist, 0.125 mmol/kg) and Evans Blue (EB) 2% (2 mg/kg) were injected intravenously. T1-weighted images were acquired post gadolinium. To demonstrate the effect of the microcatheter tip placement, the microcatheter was withdrawn more proximally within basilar artery inside the MR scanner, after which the Feraheme and mannitol infusions were repeated.
Results: DSC MRI of IA Feraheme boluses allowed real-time assessment of local parenchymal perfusion, manifested as MRI signal reduction (hypointensity). Rapid Feraheme washout with clearance of the hypointensities immediately after the bolus allowed for repetitive boluses at different speeds with subsequent DSC imaging to optimize injection rate and microcatheter location to achieve the desired perfusion territory.
The rate of injection greatly affected the perfusion area with slower rates producing a smaller, localized region and faster speeds resulting in a larger, more diffuse territory. Notably, a given injection rate resulted in different ranges of perfusion territories in different rabbits, necessitating personalized titration of injection speed to achieve the desired targeted area for each rabbit.
The microcatheter tip position in the vertebro-basilar circulation also greatly affected the perfusion area with distribution to the medulla, cervical spinal cord, and adjacent paraspinal muscles when in the V4 segment, whereas a position in the mid basilar artery resulted in supply to the pons, medulla and cerebellum. Importantly, even small changes in the microcatheter tip position within the basilar artery resulted in differential perfusion of the brainstem based on the tortuosity and direction of flow within the basilar artery. The territory of BBB opening depicted in vivo by gadolinium-enhancement and post mortem Evans Blue staining closely matched the perfusion area.
Conclusions: DSC perfusion imaging, allows for the dynamic depiction of transcatheter parenchymal flow, which in turn enables the prediction and titration the area of BBBO.
965
BRAIN-0754
Non-Registered Abstracts
Non-Registered Abstracts
LONG-TERM SURVIVAL AND DIFFERENTIATION OF HUMAN NEURAL STEM CELLS IN THE ISCHEMIC STROKE BRAIN OF RHESUS MONKEY WITHOUT IMMUNOSUPPRESSION
Y. Jin1, S Lee1, H Lee2, Y Lee1, K Yi3, K Jeong1, C Jeon1, H Yeo1, S Cha3 and K Chang1
1National Primate Research Center, Korea Research Institute of Bioscience & Biotechnology, Cheongju-si, Korea
2Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea
3Department of Radiology, Chungbuk National University College of Medicine, Cheongju-si, Korea
Abstract
Globally, Stroke was one of the third largest causes of human death in 2012. Also, life lost rates for stroke increased by 12% between 2000 and 2012. Ischemic stroke accounts for approximately 70 ∼ 80% of stroke. However, ischemic stroke therapies are limited, the majority of ischemic stroke patients are needed alternative treatment. Stem cell transplantation therapy may have great potential to therapeutic strategy in ischemic stroke. In the present study, we inoculated human neural stem cells (hNSCs) in ischemic stroke model of two non-human primate rhesus monkeys brain via the middle cerebral artery and femoral vein without immunosuppression. During 24 months after hNSCs xenograft, we evaluated of hNSCs’s survival, differentiation, potential tumorigenesis via magnetic resonance imaging (MRI), histopathological and immunohistochemical analyses. In conclusion, xenografted hNSCs in ischemic stroke model of two monkeys survived successfully for 24 months in the absence of immunosuppression and also were differentiated into neurons and astrocytes. Their long term survival was identifiable with the use of fluorescent magnetic nanoparticles s by MRI follow-up. MRI, histopathological, and immunohistochemical analyses at 24 months post inoculation showed no evidence of tumor formation by the grafted hNSCs. When compared to the results in injection of hNSCs by the middle cerebral artery and femoral vein two kinds of paths, the path of middle cerebral artery was identified as methods to deliver a large number of hNSCs in the brain than in the paths of femoral vein.
966
BRAIN-0028
Non-Registered Abstracts
Non-Registered Abstracts
TRANSCRANIAL DOPPLER ULTRASONOGRAPHY: A METHOD OF EVALUATING COGNITIVELY IMPAIRED AND NON-COGNITIVELY IMPAIRED ELDERLY
M. Kalbi1, J Catindig1, S Marasigan1 and J Navarro1
1Neurology, Jose R. Reyes Memorial Medical Center, Metro Manila, Philippines
Abstract
Introduction: Aging and dementia are associated with changes in cerebrovascular structure and function which contribute to cognitive decline. Research investigating functional cerebrovascular have employed techniques such as functional magnetic resonance imaging, positron emission tomography or single photon emission computed tomography but these techniques are expensive and are not available in tertiary government hospitals in the Philippines. Transcranial Doppler Ultrasonography (TCD) is a non-invasive, inexpensive and portable technique that can successfully assessed the intracranial hemodynamics of an aging brain.
Objective: The purpose of this study was to investigate and compare the cerebral hemodynamic status (blood flow velocity and pulsatility index) of cognitively impaired and non-cognitively impaired elderly using Transcranial Doppler.
Methods: This is a cross sectional study conducted in Jose R. Reyes Memorial Medical Center (JRRMMC) from January to August 2013. Forty patients were selected using convenience sampling and were screened using the Montreal Cognitive Assessment-Philippines (MoCA-P). Scores more than or equal to 21 were grouped under non-cognitively impaired elderly while scores lower than 21 were under cognitively impaired elderly. Transcranial ultrasound basal examination were performed using a 2-MHz power motion probe (M-mode) to study the middle cerebral artery (MCA), the anterior circulation artery (ACA) and posterior cerebral artery (PCA).
Results: Our findings showed that patients with cognitive impairment have lower mean flow velocity (p value = 0.0001) and higher pulsatility index (p value = 0.0001) when compared to non-cognitively impaired elderly.
Conclusion: Our findings are congruent with previous observations that abnormalities in cerebral hemodynamic status are present in cognitively impaired elderly and may be related to microvessel damage secondary to vascular risk factors.
967
BRAIN-0029
Non-Registered Abstracts
Non-Registered Abstracts
PREVALENCE OF INTRACRANIAL STENOSIS USING TRANSCRANIAL DOPPLER AND ITS DIAGNOSTIC ACCURACY IN VERTEBROBASILAR INFARCTION
M. Kalbi1 and J Navarro1
1Neurology, Jose R. Reyes Memorial Medical Center, Metro Manila, Philippines
Abstract
Introduction: Posterior circulation ischemia is an important cause of acute neurological disease. Therefore, emergent non assessment of posterior circulation is critical not only for rapid confirmation of but also for identification of patients at higher risk of poor outcome as candidates for interventional treatment. Transcranial Doppler (TCD) is a fast, non invasive, widely available diagnostic tool that can detect, localize and grade the severity of intracranial arterial obstruction in the setting of acute ischemic stroke.
Objective: The objectives of this study were to determine the prevalence rate of intracranial stenosis using Transcranial Doppler (TCD) among patients with vertebrobasilar ischemia and to evaluate the diagnostic accuracy of TCD compared with brain Magnetic Resonance Angiography (MRA) in the detection of intracranial stenosis.
Methods: This is a prospective study conducted in Jose R. Reyes Memorial Medical Center (JRRMMC) Neurology Ward from January 2012 to December 2012. Consecutive patients admitted to the ward with definite clinical diagnosis of acute vertebrobasilar ischemia underwent TCD and brain MRI with MRA done 48 hours after admission. A second TCD was done one week after admission. SONIA criteria for mean flow velocity (MFV) cutoffs on TCD were used for identification of > 50 % stenosis.
Results: Twenty patients were included in the study. Results showed that 75 % (15 out of 20) of patients with vertebrobasilar infarctions have intracranial stenosis in MRA. Out of the 15 patients with vertebrobasilar stenosis detected by MRA, 6 of them registered high mean flow velocity on TCD. TCD showed high specificity (100%) but less sensitivity (40%) in the detection of vertebrobasilar stenosis.
Conclusion: TCD can be suggested as a screening tool in detecting intracranial stenosis in patients with acute vertebrobasilar infarctions.
968
BRAIN-0814
Non-Registered Abstracts
Non-Registered Abstracts
NEURAL CORRELATES OF UNFAMILIAR VERSUS SELF-SELECTED MUSIC GENRES INVESTIGATED WITH FMRI TOWARDS DEVELOPING AN OPTIMIZED PARADIGM FOR MUSIC THERAPY
C. Karmonik1, F Brooks2, J Anderson3, A Brandt4, S Fung5 and JT Frazier2
1MRI Core, Houston Methodist Research Institute, Houston, USA
2Center for Performing Arts Medicine, Houston Methodist Hospital, Houston, USA
3MRI Core, Houston Methodist Hospital Research Institute, Houston, USA
4Shepard School of Music, Rice University, Houston, USA
5Radiology, Houston Methodist Hospital, Houston, USA
Abstract
Purpose: To investigate if differences in brain activation when listening to unfamiliar music pieces compared self-selected music with emotional attachment can be utilized to develop a personalized music therapy paradigm.
Methods: fMRI BOLD activation using the generalized linear model (GLM) was quantified in 12 healthy subjects (4 male) listening to 3 music pieces and 3 control spoken-word sections (each 6 minutes, alternating 30 seconds off/on, 3T Philips Ingenia, TR = 2.4 seconds) while simultaneously undergoing recording of EEG brain signals (Brainvision, 16 bipolar electrodes). Subjects were instructed to bring one music piece to the session with strong emotional attachment. Unfamiliar pieces included Bach invention #1 and traditional Japanese court music (‘Gagaku’). As controls, sonorous African click language (‘Click’), emotional speech (‘The Great Dictator’, Charlie ‘Chaplin’) and a collection of audio news casts of non-emotional speech (‘Cronkite’) was included. Bach invention #1 was repeated with visual guidance by a moving cursor through the score sheet.
Results: Brain waves recorded with EEG indicated awareness in all subjects for all paradigms. In addition to sensory areas, self-selected music showed statistical significant (p
Conclusion: Varying degrees of familiarity and emotional attachment when listening to music results in distinct variations in brain activation. Visual guidance increased activation during listening. These individual differences in music processing may be of importance when selecting music for use in therapy to optimize outcome.
.
969
BRAIN-0905
Non-Registered Abstracts
Non-Registered Abstracts
CALCIUM CHANNEL BLOCKER ENHANCES BENEFICIAL EFFECTS OF AN ANGIOTENSIN II AT1 RECEPTOR BLOCKER AGAINST CEREBROVASCULAR-RENAL INJURY IN TYPE 2 DIABETIC MICE
Recentclinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calciumchannel blockers (CCBs) elicits beneficial effects on cardiovascular and renalevents in hypertensive patients with high cardiovascular risks. In the presentstudy, we hypothesized that CCB enhances the protective effects of anangiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renalinjury. Saline-drinking type 2 diabetic KK-Ay mice developedhypertension and exhibited impaired cognitive function, blood-brain barrier(BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. Thesebrain and renal injuries were associated with increased expression of NADPHoxidase components and oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) and hydralazine (25 mg/kg/day) similarly reduced blood pressure insaline-drinking KK-Ay mice. However, treatment with olmesartan, butnot with hydralazine, attenuated cognitive decline, BBB disruption, glomerularinjury and albuminuria, which were associated with a reduction in oxidativestress in brain and kidney tissues. Furthermore, a suppressive dose ofazelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associatedcerebrovascular-renal protective effects, independent of blood pressurereduction in type 2 diabetes.
970
BRAIN-0706
Non-Registered Abstracts
Non-Registered Abstracts
FUNCTIONAL ULTRASOUND (FUS) IMAGING OF BRAIN HEMODYNAMICS IN A RAT MIDDLE-CEREBRAL ARTERY OCCLUSION (MCAO) MODEL OF SELECTIVE NEURONAL LOSS (SNL) MIMICKING TRANSIENT ISCHEMIC ATTACK (TIA)
C Dussaux1, C Brunner1, C Isabel1, A Martin2, A Savoye1, G Montaldo1 and JC Baron1, A. Urban1
1Psychiatry and Neurosciences Center - Team Optogenetics and Brain Imaging INSERM U894, Sainte- Anne Hospital, Paris, France
2Molecular Imaging Unit, CICbiomaGUNE, San Sebastian, Spain
Abstract
Objectives: SNL is a known outcome of brief MCAo in rodents, affecting mainly the striatum or cortex with proximal and distal MCAo, respectively[1]. SNL is important as it might also occur after TIAs, potentially impacting the cognitive and plastic ‘reserve’. However, both the behavioral and tissue perfusion changes underlying SNL remain only partly understood. In the present study, we assessed SNL and behavior in rodents in conjunction with fUS, a new imaging method for longitudinal whole-brain mapping of cerebral blood volume (CBV) with high spatiotemporal resolution[2].
Methods: Eight adult Sprague-Dawley rats were subjected to 45 min MCAo under 1.5% isoflurane and 100% oxygen. Four sham rats were used as controls. fUS data were acquired through previously thinned skull, serially before, during and at 3 and 6 days after reperfusion. Ipsilateral/contralateral CBV ratios (CBVr) were computed for a template of atlas-based cytoarchitectonic ROIs modified from previous work[3]. The Neuroscore and subtle sensorimotor functions (modified Sticky Label test and Beam Walking test) were assessed before and serially after tMCAo. Brains were collected at day 21 for immunofluorescence (IF) using NeuN, Iba1 and GFAP.
Results: We observed a marked (>50%) reduction in CBVr in the MCA territory during occlusion in 7/8 rats (one rat with no CBVr decrease was excluded from further analysis). Maximal CBVr reduction affected the somatosensory cortex (79 ± 13% relative to baseline; p < 0.0001). CBVr had returned to near-baseline 15 mins after reperfusion, and to normal levels subsequently (p < 0.05, ANOVA). No statistically significant behavioral effects emerged across the group at any time point. No changes in CBVr or behavior were present in sham rats. There was marked striatal SNL (associated with moderate microglial activation and marked astrocytosis) in 5/7 MCAo rats vs 0/4 sham (p < 0.05), and mild cortical SNL was present in 4/7 MCAo rats (and 1/4 shams). There was no correlation among CBV, behavioral scores and IF lesion volumes.
Conclusions: This study shows the feasibility of fUS to serially map CBV during and over days following MCAo. Mild and less consistent cortical SNL occurred despite marked initial rCBV reductions. The lack of behavioral correlates with mainly striatal SNL contrasts with cortical SNL[4] and is consistent with previous reports regarding striatal infarcts[5]. Overall, SNL is a frequent sequelae of brief MCAo in rodents and likely also occurs after TIAs, and as such has potential clinical and therapeutic relevance.
References
J.C. Baron et al, JCBFM, 34 (2014) 2–18.A. Urban et al, Neuroimage, 101 (2014) 138–49.J.L. Hughes et al, Neuroimage, 49 (2010) 19–31.Ejaz S. et al, Stroke (in press).S. Wegener et al, J Magn Reson Imaging, 21 (2005) 340–6.
971
BRAIN-0176
Non-Registered Abstracts
Non-Registered Abstracts
CROSS-TALK BETWEEN GONADAL STEROID HORMONES SIGNALING AND CYTOKINE SIGNALING AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY
M. Khaksari Haddad1, F Frahani2, S Dabiri3, M Nikpour4 and R Khaksari Haddad4
1Physilogy Research Center, Kerman University of Medical Sciences, kerman, Iran
2Neurosciences Research CenterInstitute of Neuropharmacology, Kerman University of Medical Sciences, kerman, Iran
3Department of Pathology, Kerman University of Medical Sciences, kerman, Iran
4Physiology Research Center, Kerman University of Medical Sciences, kerman, Iran
Abstract
Objectives:The neuroprotectiveand anti-inflammatory effects of female steroid hormones on traumatic brain injury (TBI)are mediated, in part, by inhibitory effects on cytokines (Sarkaki et al., 2013; Khaksari et al., 2011)levels after TBI. In addition to the above mechanism, where it is reported that these steroids may affect the cytokine signaling pathway (Liu et al., 2014), to determine this mechanism by which steroids regulates this signaling pathway, here we investigated the effects of administration of exogenous estrogen/progesteroneon brain STAT3/SOCS3 in female rats after TBI.
Methods: In this study, ovariectomized female rats were randomly divided into 7 groups: (1) sham, (2) TBI group,(3) vehicle, (4) estrogen low concentrations (E1), (5) estrogenhighconcentrations (E2), (6) progesteronelow concentration (P1), and (7) progesteronehigh concentration (P2). The TBI model was established using a Marmarou ‘sweight-dropping model. Brain samples were extracted 24 h following TBI. The expression levels of STAT3and SOCS3were examined using immunohistochemistry, and brain edema was determined using brain water content (BWC).
Results:This model consistently resulted in increased BWC. Both steroid hormones attenuated post injury brain edema. In TBIgroup, theSOCS-3 positive cells, compared toshamdecreased and inallgroups thattreated withestrogenor progesterone, these SOCS-3 positive cells were increased; but this increaseinE1, E2, and P2 groups compared to vehicle groupwas statistically significant. Although comparisons between treatment groups showed that E2 effectcompared with E1 and P2 groups was significant. The p-STAT3 positive cells significantly decreased after TBI. However, only E2increased p-STAT3 activation, That a greater inhibitory effect of E2 on neuronscompared with astrocytes or microglia.
Conclusion.These results suggest that exogenous estrogen/progesteroneincrease brainSOCS3 activation and decreasep-STAT3 level after TBI. This represents the initial demonstration offemale steroid hormones crosstalk with cytokines signaling in post injury brain.
References
SarkakiARKhaksari HaddadMShahrokhiN. Time- and Dose-Dependent Neuroprotective Effects of Sex Steroid Hormones on Inflammatory Cytokinesafter a Traumatic Brain Injury. J. Neurotrauma2013; 30: 47–54.KhaksariMShahrokhiNMoshtaghiGAsadikaramG. The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury. Can J PhysiolPharmacol2011; 89(1): 31–40.LiuCJKuoFCHuHMChenCYHuangYBChengKHYokoyamaKKWuDCHsiehSKuoCH. 17β-Estradiol inhibition of IL-6-Src and Cas and paxillin pathway suppresses human mesenchymal stem cells-mediated gastric cancer cell motility. Transl Res2014; 164(3): 232–43.
972
BRAIN-0015
Non-Registered Abstracts
Non-Registered Abstracts
FOCAL TRIPHASIC SHARP WAVES AND SPIKES IN THE ELECTROENCEPHALOGRAM
A Janati1 and N Alghassab2, U. Khan3
1Neurology, Center for Neurology, Fairfax, USA
2Neurology, King Khalid Hospital, Ha'il, Saudi Arabia
3Neurology, Dow University of Health Sciences, Karachi, Pakistan
Abstract
Objective: There is a plethora of data in the EEG literature on the characteristics of the most prominent component of interictal epileptiform discharges (IED), namely the negative (fast) phase. Surprisingly, however, little attention has been drawn to the after-coming slow wave (ASW), and its pathological as well as clinical significance. In this paper, we will address the significance of prominent (high amplitude) ASW, giving rise to a triphasic morphology of the IED (focal triphasic sharp waves and spikes-FTSW). We will discuss this EEG pattern with respect to its clinical, neurophysiological, and neuropathological significance.
Method: This investigation was conducted on a heterogeneous group of patients at KKH, Ha'il, KSA.
Result: Our data revealed that FTSW were rare EEG events occurring primarily in the first two decades of life. Ninety percent of the patients with FTSW had epilepsy, presenting clinically with generalized convulsive seizures, often without partial onset. The majority of these patients responded favorably to anticonvulsant monotherapy. We were surprised to find that half of the patients with FTSW had chronic and/or static CNS pathology, particularly congenital CNS anomalies. Even though more than one mechanism may be involved in the pathogenesis of FTSW, we believe a deeply seated pacemaker as the source of this EEG pattern is the most compelling theory.
Conclusion: The presence of FTSW should alert clinicians to the possibility of an underlying chronic and/or static CNS pathology, in particular congenital CNS anomalies, underscoring the significance of neuroimaging in the work-up of this population. Moreover, it is conceivable that the prominent ASW may contribute to the interictal intellectual dysfunction of these patients, justifying aggressive anticonvulsant therapy.
References
Amer Clin Neurophysiology Society. Guideline 8: guidelines for recording clinical EEG and digital media. J Clin Neurophysiol2006; 23(2): 122–124.BlumeWT. Pathogenesis of Lennox–Gastaut syndrome: considerations and hypotheses. Epileptic Disord2001; 3(4): 183–196.BlumenfeldH. Cellular and network mechanisms of spike-wave discharges. Epilepsia2005; 46(Suppl. 9): 21–33.CambierDMKantarciKWorrellGA. Lateralized and focal clinical, EEG and FLAIR MRI abnormalities in Jacob–Creutzfelt disease. Clin Neurophysiol2003; 114(9): 1724–1728.ChatrianGEBergaminiLDondeyM. A glossary of terms most commonly used by clinical electroencephalographers. Electroencephalogr Clin Neurophysiol1974; 37: 538–548.Daube JR, Stead SM (2009) Basics of neurophysiology. In: Daube JR, Rubin DI (eds) Textbook of clinical neurophysiology, 3rd edn, Oxford, pp 69–96.EbersoleJS. Defining epileptogenic foci: past, present, future. J Clin Neurophysiol1997; 14(6): 470–483.FischFJ. Interictal epileptiform activity: diagnostic and behavioral implications. J Clin Neurophys2003; 20(3): 155–162.FoleyJMWatsonCWAdamsRD. Significance of the electroencephalographic changes in hepatic coma. Trans Am Neurol Assoc1950; 75: 161–165.GolensohnESPurpuraDP. Intracellular potentials of cortical neurons during focal epileptogenic discharges. Science1963; 139: 840–842.JanatiAErbaG. Electroencephalographic correlates of near-drowning encephalopathy in children. Electroencephalogr Clin Neurophyiol1982; 53(2): 182–191.JanatiAHusainMMMooreDB. Suppression-burst pattern associated with generalized epileptiform discharges and alpha-theta pattern coma. Clin Electroencephalogr1986; 17: 82–88.KabatJKralP. Focal cortical dysplasia. Pol. J Radiol2012; 77(2): 35–43.
973
BRAIN-0016
Non-Registered Abstracts
Non-Registered Abstracts
POSITIVE SHARP WAVES IN THE EEG OF CHILDREN AND ADULTS
A Janati1, U. Khan2, N Alghassab3 and K Alshurtan3
1Neurology, Center for Neurology, Fairfax, USA
2Neurology, Dow University of Health Sciences, Karachi, Pakistan
3Neurology, King Khalid Hospital, Ha'il, Saudi Arabia
Abstract
Objective: Interictal epileptiform discharges (IEDs) with negative polarity have been extensively studied in the EEG literature. However, little attention has been drawn to IED with positive polarity [positive sharp waves (PSWs)]. In this paper, we discuss pathophysiological, neuroimaging, and clinical correlates of this pattern in a heterogeneous group of children and adults who demonstrated PSW in their scalp EEG.
Method: We prospectively reviewed the EEGs of 1,250 patients from a heterogeneous population over a period of 1 year.
Results: Thirty-one patients had PSW in their EEG. We documented EEG parameters as well as demographic, clinical, and neuroimaging data. Statistical analysis was performed to correlate the aforementioned data. The analysis showed that PSW is an epileptogenic pattern with localizing significance, occurring primarily in the younger age groups. Furthermore, there was a strong association of PSW with chronic and/or static CNS pathology, in particular, congenital CNS anomalies, often accompanied by psychomotor retardation. Patients with “multifocal'' PSW invariably exhibited severe intellectual and motor deficits associated consistently with a variety of congenital CNS insults.
Conclusion: PSW is a rare and under-reported EEG abnormality which, similar to negative IED, signifies focal epileptogenecity. The presence of PSW should prompt neuroimaging studies to investigate an associated chronic/static CNS pathology, in particular, congenital CNS anomalies. This association is particularly strong when PSW is multifocal in which case patients present with severe intellectual and motor deficits.
References
American Clinical Neurophysiological Society. Guideline 8: guidelines for recording clinical EEG and digital media. J Clin Neurophysiol2006; 23(2): 122–124.BlumeWT. Pathogenesis of Lennox–Gastaut syndrome: considerations and hypotheses. Epileptic Disord2001; 3(4): 183–196.Brazier MBA (1951) A study of the electrical fields at the surface of the head. Electroencephalogr Clin Neurophysiol: 38–52.ChatrianGEBergaminiLDondeyM. A glossary of terms most commonly used by clinical electroencephalographers. Electroencephalogr Clin Neurophysiol1974; 37: 538–548.EbersoleJS. Defining epileptogenic foci: past, present, future. J Clin Neurophysiol1997; 14(6): 470–483.GoldensohnESPurpuraDP. Intracellular potentials of cortical neurons during focal epileptogenic discharges. Science1963; 139: 840–842.KabatJKralP. Focal cortical dysplasia. Pol J Radiol2012; 77(2): 35–43.Kellaway P, Hrachovy RA. Electroencephalography. In: Swaiman KF, Wright FS (eds) The practice of pediatric neurology, 2nd edn, pp 96–114.Lombroso CT (1981) Intracranial hemorrhage in the newborn. A prospective clinical and electrophysiological study of 37 cases. In: Proceedings of the IYDP commemorative International Symposium on developmental disabilities. Elsevier, Tokyo, pp 251–56.LombrosoCT. Neonatal polygraphy in full term and premature infants: a review of normal and abnormal findings. J Clin Neurophysiol1985; 2: 105–155.McCullochW. Mechanisms for the spread of epileptic activation of the brain. Electroencephalogr Clin Neurophysiol1972; 32: 529–544.MaulsbyRL. Some guidelines for assessment of spikes and sharp waves in EEG tracings. Am J EEG Technol1971; 11: 3–16.MatsuoFKnottJR. Focal positive spikes in electroencephalography. Electroencephalogr Clin Neurophysiol1977; 42: 15–25.NowackWJJanatiAAntuagoT. Positive temporal sharp waves in the neonate. J Clin Neurophysiol1987; 4: 315–317.NowackWJJanatiA. Positive sharp waves in neonatal EEG. Am J EEG Technol1990; 30: 211–221.
974
BRAIN-0946
Non-Registered Abstracts
Non-Registered Abstracts
THE EFFECTS OF EXPOSURE TO 915 MHZ RADIOFREQUENCY IDENTIFICATION ON CEREBRAL GLUCOSE METABOLISM IN RAT: A [F-18] FDG MICRO-PET STUDY
H. Kim1, Y LEE2, Y An3, M Paik4, H Choi5, J Pack6, N Kim7 and Y Ahn1
1Department of Neurosurgery, Ajou University School of Medicine, Suwon, Korea
2Division of Life Science and Pharmaceuticals College of Pharmacy, Ewha Woman's University, Seoul, Korea
3Department of Nuclear Medicine, Ajou University School of Medicine, Suwon, Korea
4College of Pharmacy, Sunchon National University, Sunchon, Korea
5Department of Nuclear Medicine, Electronics and Telecommunications Research Institute, Daejeon, Korea
6Department of Radio Sciences and Engineering College of Engineering, Chungnam National University, Daejeon, Korea
7School of Electrical and Computer Engineering, Chungbuk National University, Cheongju, Korea
Abstract
Purpose: We investigated the effect of whole-body exposure to 915-MHz radiofrequency identification (RFID) on rat cortical glucose metabolism by using (18)F-deoxyglucose positron emission tomography (FDG-PET).
Materials and methods: Male Sprague-Dawley rats were divided into three groups: Cage-control, sham-exposed and RFID-exposed groups. Rats were exposed to the 915-MHz RFID for 8 h daily, 5 days per week, for 2 or 16 weeks. The whole-body average specific absorption rate (SAR) was 4 W/kg for the field of the 915 MHz RFID signal. FDG-PET images were obtained the day after RFID exposure, using micro-PET with a FDG tracer. With a Xeleris functional imaging workstation, absolute values in regions of interest (ROI) in the frontal, temporal and parietal cortexes and cerebellum were measured. Cortical ROI values were normalized to the cerebellar value and compared.
Results: The data showed that the relative cerebral glucose metabolic rate was unchanged in the frontal, temporal and parietal cortexes of the 915 MHz RFID-exposed rats, compared with rats in cage-control and sham-exposed groups.
Conclusion: Our results suggest that 915 MHz RFID radiation exposure did not cause a significant long lasting effect on glucose metabolism in the rat brain.
975
BRAIN-0214
Non-Registered Abstracts
Non-Registered Abstracts
NEUROTOXICITY OF CASSAVA CYANOGENS: RELEVANCE TO THE PATHOGENESIS OF KONZO, A MOTOR NEURON DISEASE PREVALENT IN SUB-SAHARAN AFRICA
S. Kimani1, S Kipruto2, FR.E.D Bukachi3, V Monterroso4, C Maitai5 and D Tshala-Katumbay6
1Nursing, University of Nairobi, Nairobi, Kenya
2Pharmacology and Pharmacognosy, University of Nairobi, Nairobi, Kenya
3Medical Physiology, University of Nairobi, Nairobi, Kenya
4Laboratory animal services, Georgia Regents University, Georgia, USA
5Pharmacology and Pharmacognosy, University Of nairobi, Nairobi, Kenya
6CROET, Oregon Health and Science University, Portland, USA
Abstract
Background: Cassava is staple food toover half a billion people globally. Consumption of insufficiently processedcassava and dietary sulfur amino acid (SAA) deficiency has been implicated inthe pathogenesis of Konzo, a paralytic condition prevalent in Sub-Saharancountries. Recently cyanogenic cassava has been associated with cognitivedeficits in humans. The probable candidates for such neurodegeneration and/ordisability include cyanide, or cyanate, sulfur deficiency, or their respectivecombinations. The susceptibility factors and mechanisms underlying the toxicityof cyanogenic cassava have remained poorly understood.
Objectives: To elucidate themolecular neuro-targets of cassava cyanogens (cyanide or cyanate) toxicityunder SAA-deficient diet in rodents.
Methods: Young adult male rats(Crl: NIH-Fox1 rnu/Fox 1+, 6–8 weeks old) were fed either a diet rich in allamino acids (AAA) or 75%-deficient in SAA and treated intraperitoneally witheither 2.5 mg/kg/body weight (bw) NaCN, or 50 mg/kg/bw NaOCN, or 1 µl/g/bwsaline, for up to 6 weeks. Behavioral activity and protein carbamoylation wereassessed. Carbamoylation of albumin and spinal cord proteins was analyzed byliquid chromatography mass spectrometry (LC-MS/MS).
Results: Rats treated with NaCN showed acute seizures whereas NaOCN induced limb paralysisunder SAA-restricted diet. Additionally, NaOCN induced high levels ofcarbamoylation relative to NaCN and vehicle (P < 0.001). At Day 14, adiet-treatment interaction effect on albumin carbamoylation (p = 0.07) was found, however there was no effect attributed to diet (p = 0.71) at day 28. The meannumber of NaCN-associated carbamoylated sites on albumin became 47.4%significantly higher relative to vehicle (95% CI:16.7–86.4%) at day 28. Spinalcord proteins were only carbamoylated by NaOCN prominently under theSAA-restricted diet. Differentially carbamoylated proteins included myelinbasic protein, myelin proteolipid protein, neurofilament light polypeptide, glial fibrillary acidic protein, and 2', 3' cyclic-nucleotide3'-phosphodiesterase.
Conclusion: The nervous systemsusceptibility to food (cassava) cyanogenesis and neurotoxic insults seen inkonzo subjects may result from a “multiple hit” process including cyanide, cyanate toxicity, deficiency in sulfane sulfur, and cyanate-induced carbamoylation. The multiple hit processes may combine direct mitochondrial insults, proteincarbamoylation and a thiol-redox derangement. This level of pathogenetic complexity should be considered in biomarkerstudies and efforts to prevent neurotoxicity effects of cassava.
976
BRAIN-0113
Non-Registered Abstracts
Non-Registered Abstracts
PROPHYLACTIC AND PROLONGED HYPOTHERMIA IN POOR-GRADE-SAH REDUCES DEGREE OF VASOSPASM AND RATE OF DELAYED CEREBRAL INFARCTIONS
JB Kuramatsu1, R Kollmar1, D Staykov1, SP Kloska2, A Doerfler2, IY Eyüpoglu3 and S Schwab1, H.B. Huttner1
1Department of Neurology, University Hospital Erlangen, Erlangen, Germany
2Department of Neuroradiology, University Hospital Erlangen, Erlangen, Germany
3Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany
Abstract
Background: Therapeutic hypothermia (TH) is an established neuroprotective approach after cardiac arrest and growing evidence supports TH as supportive treatment in stroke. In subarachnoid haemorrhage (SAH) only few data exists comprising heterogeneous TH-strategies. We evaluated a novel approach of prophylactic and prolonged TH and its influence on key complications in poor-grade SAH - vasospasm and delayed cerebral infarction (DCI).
Methods: This observational matched-controlled study included 36 poor-grade (Hunt&Hess-Scale > 3, WFNS-Scale > 3) SAH patients. Twelve patients received prophylactic TH ( < 48 h after ictus), mild (35℃), prolonged (7 ± 1days), and were matched to 24 patients from prospective SAH-database. Vasospasm was diagnosed by angiography, serially evaluated by Doppler-sonography and DCI was defined as new infarction on follow-up-CT. Functional outcome was assessed at 6-months by modified-Rankin-Scale and categorized as favorable (mRS = 0–2) versus unfavorable (mRS = 3–6) outcome.
Results: Vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of vasospasm as well as peak-spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH versus 50% in TH-treated patients, translating into a relative risk reduction of 43% with an risk-ratio of 0.33 (CI(0.14–0.77);p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7% versus 33.3% of non-TH (p = 0.06).
Conclusion: Prophylactic and prolonged TH seems to influence degree of vasospasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising therapy targeting the multiple pathways of DCI development, notably vasospasm, which strongly warrants further evaluation of its clinical impact.
977
BRAIN-0038
Non-Registered Abstracts
Non-Registered Abstracts
PREDICTION OF PROGRESSIVE SECONDARY BRAIN DAMAGE FOLLOWING TRAUMATIC INTRACRANIAL HEMORRHAGE
J. Kuzibaev1 and K Makhkamov1
1Neurosurgery, Republican Research Center of emergency medicine, Tashkent, Uzbekistan
Abstract
Introduction: Traumatic intracranial hemorrhage (TIH) represents a challenge for neurosurgeons due to its high mortality and morbidity rates. The most severe lesion associated with TIH is secondary brain damage. Thus, the purpose was to investigate the CT parameters for predicting of progressive secondary brain damage (PSBD) associated with TIH.
Method: We reviewed the records of 252 patients suffering from TIH whose first CT scan was Obtained within 24 h of the injury. The repeat CT examinations were routinely Obtained within 24 h of admission as well as when suggested by clinical worsening. The patients were divided into two groups: PSBD group (124 patients) and non- PSBD group (128 patients). All patients in two groups were comparable due to the level of consciousness and ages of patients and severity of secondary brain injury.
Results: The differences between PSBD and non- PSBD were significant in the initial CT scans showing type, volume and location of TIH, brain swelling and midline shift as well as the associated brain contusion (P < 0.01). Logistic regression analysis showed that early predictors of PSBD were: intracerebral type of hemorrhage, temporal localization of hematoma, volume of hematoma more than 40 cm3, midline shift more than 5 mm, brain swelling and contusion volume more than 20 cm3 (P < 0.01).
Conclusions: Thus, if the initial CT scan of patients with TIH shows intracerebral hemorrhage, temporal localization of hematoma, volume of hematoma more than 40 cm3, midline shift more than 5 mm, brain swelling and contusion volume more than 20 cm3, an earlier CT scan should be performed for detection of PSBD.
978
BRAIN-0039
Non-Registered Abstracts
Non-Registered Abstracts
TREATMENT OF SECONDARY BRAIN DAMAGE IN PATIENTS WITH TRAUMATIC INTRACRANIAL HEMATOMAS USING DECOMPRESSIVE CRANIECTOMY
J. Kuzibaev1 and K Makhkamov1
1Neurosurgery, Republican Research Center of emergency medicine, Tashkent, Uzbekistan
Abstract
Introduction: OBJECTIVE: Traumatic intracranial hematomas represent a challenge for neurosurgeons due to their high mortality and morbidity. Secondary brain damage is an important factor that influences the outcome of traumatic intracranial hematomas. We compared the effect of early decompressive craniectomy with that of non- decompressive craniectomy on the outcome of patients with secondary brain damage following severe traumatic brain injury.
Method: A retrospective review was conducted of 127 consecutive patients who presented with secondary brain damage following isolated severe head injury with intracranial hematomas. Early decompressive craniectomy after hematoma removal (mean time from injury: 5.8 ± 2.5 h) was carried out in 82 patients (mean age: 45.7 ± 5.6 years), whereas 45 patients (mean age: 43.4 ± 4.1 years) were underwent only hematoma removal without decompressive craniectomy (mean time from injury: 6.1 ± 3.1 h). All patients in two groups were comparable due to the level of consciousness of patients, volume and localization of hematoma, severity of secondary brain injury and axial dislocation of middle brain structures.
Results: Due to postoperative CT results volume of secondary brain injury zone was reduced 2.4 times more in patients who underwent early decompressive craniectomy compared with the patients without decompressive craniectomy. Axial dislocation of middle brain structures was decreased from 11.4 ± 3.7 mm to 1.8 ± 0.8 mm in the early decompressive craniectomy group, and from 8.9 ± 4.5 mm to 4.4 ± 2.5 mm in non-decompressive craniectomy group.
Conclusions: Early decompressive craniectomy, employed prior to the onset of irreversible ischemic changes, may be an effective method of treating the secondary deterioration from secondary brain damage following severe head injury with intracranial hematomas.
979
BRAIN-0324
Non-Registered Abstracts
Non-Registered Abstracts
A BIOMARKER PANEL TO RULE-OUT UNNECESSARY CT-SCANS IN MILD TRAUMATIC BRAIN INJURY (MTBI)
L. Lagerstedt1, N Tiberti2, N Turck1, E Andereggen3, A Bulla4, L Rinaldi3, A Sarrafzadeh-Khorassani5, K Schaller5 and JC Sanchez1
1Human Protein Sciences, University of Geneva, Geneva, Switzerland
2Pathology, University of Sydney, Sydney, Australia
3Emergency Center, Geneva University Hospitals, Geneva, Switzerland
4Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
5Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland
Abstract
Background: CT-scans are used to detect brain lesions due to a mild traumatic brain injury (mTBI). However, CT-scans are harmful to the patients and the majority of mTBI patients are CT negative. Despite several years of research, no blood biomarker has yet been found to drastically reduce the number of CT-scans. The protein S100b, with approximatively 30% specificity and almost 100% sensitivity, remains the most promising biomarker. The proteins GSTP1 (glutathione S-transferas pi), NDKA (nucleoside diphosphate kinase A) and H-FABP (heart-type fatty acid binding protein) have previously been discovered in brain injury models. Here, we investigated if these proteins individually or together as a panel could perform better than the S100b to rule-out unnecessary CT-scans.
Methods: mTBI patients (n = 87) were recruited within 6 h after trauma and their plasma levels of S100b, GSTP1, NDKA and H-FABP were measured using ELISAs. Statistical analyses, on patients dichotomized into CT-positive and CT-negative groups, were performed using Mann-Whitney U test, ROC curves and Panelomix.
Results: GSTP and S100b were significantly increased in CT positive patients (p < 0.05). The S100b had the best individual performance (sensitivity: 100% and specificity 34%). However, when S100b, GSTP and H-FABP were assembled together in a panel they were capable of reaching 58% specificity and 100% sensitivity.
Conclusions: This study demonstrated that S100b, GSTP and H-FABP combined in a panel could be a useful tool to rule-out unnecessary and harmful CT-scans.
980
BRAIN-0373
Non-Registered Abstracts
Non-Registered Abstracts
ADENOSINE 1AR TARGETED TEMPERATURE MANAGEMENT IN RATS AND RESULTANT PHYSIOLOGICAL EFFECTS OF A PHARMACOLOGICAL INDUCED HYPOMETABOLIC STATE
B. Laughlin1, K Drew1, I Bailey1 and K Dowell1
1Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, USA
Abstract
Objectives: Both hype and hope has been generated by promises of inducing suspended animation or a hypometabolic state. Biased reporting of positive results underestimates complications that ultimately limit translation to the clinic. In this study we apply the Adenosine 1A receptor (A1AR) agonist N6-Cycolhexyladenosine (CHA) in a manner similar to prior work in this lab found to induce a hibernation-like state in rats for therapeutic hypothermia. We report worse case scenarios and steps taken to avoid or manage these scenarios.
Methods: Male and female sprague-dawley rats are administered CHA via IV infusion to inhibit thermogenesis. Core body and brain temperatures, oxygen consumption, heart rate, rhythm and blood pressure are monitored throughout the experiment. Core body temperature is maintained between 30–34℃ for 24–48 hrs by adjusting the dose of CHA and/or adjusting the surface temperature of the cage via a thermoelectric cooling device we built. Side effects of bradycardia and hypotension are managed with administration of 8-SPT and norepinephrine respectively.
Results: Preliminary results indicate a pronounced individual variation in response to the CHA. Low doses of CHA resulted in bradycardia but had little to no effect on the inhibition of thermogenesis. Administration at a starting dose of 0.1 mg/kg while doubling the concentration every 4 hours resulted in the development of tolerance to the drug’s effect on thermogenesis but not bradycardia. Brain temperature follows core body temperature closely during the cooling and rewarming phases. Oxygen consumption requirements decreased after CHA administration.
Conclusion: CHA is a potent inhibitor of thermogenesis and metabolism at doses greater than 0.4 mg/kg. Variations in response and tolerance necessities close monitoring of core body temperature and administration of a loading dose. Changes in core body temperature during targeted temperature management treatment closely resemble changes in brain temperature.
References
H2S, Blackstone E, Morrison M, Roth MB. Science. 2005.’AMP (AMP), Zhang J, Kaasik K, Blackburn MR, Lee CC. Nature 2006.A1 adenosine agonist, CHA, Tupone D, Madden CJ, Morrison SF J. Neurosci. 2013.Inhibiting central pathways for thermoregulatory cold defense, Cerri et al., J Neurosci. 2013.Inhibiting the peripheral cold sensing pathway (TRPM8), Almeida et al., J Neurosci. 2012.
981
BRAIN-0913
Non-Registered Abstracts
Non-Registered Abstracts
PRO-ANGIOGENIC FUNCTIONS OF ARGININE-GLYCINE-ASPARTATE-CONTAINING OSTEOPONTIN ICOSAMER PEPTIDE VIA INTERACTING WITH AVB3 INTEGRIN
J. Lee1, Y Jin1, H Lee1, H Lee1, L Luo1 and P Han2
1Department of Anatomy, Inha University School of Medicine, Incheon, Korea
2Department of Brain and Cognitive Science, Ewha Womans University, Seoul, Korea
Abstract
Objectives: Osteopontin (OPN) is a phosphorylated glycoprotein that is secreted into body fluid after being synthesized in various cells and tissues. OPN contains arginine, glycine, aspartate (RGD)-motif, through which it binds to several cell surface integrins, that mediates a wide range of cellular processes, such as, the adhesion, migration, and survival of a variety of cell types. In the present study, authors examined the pro-angiogenic effects of a RGD-containing 20 amino acids OPN peptide (OPNpt20).
Methods: Pro-angiogenic effects of OPN icosame (OPNpt20) was examined in HUVECs and in a rat model of focal cerebral ischemia, induced by middle cerebral artery occlusion (MCAO). In HUVECs, endothelial cell proliferation, migration, and tube formation were examined in the presence or absence of OPNpt20 and pro-angiogenic processes in the postischemic brain were examined by measuring RECA-1 immunoreactivity and angiogenesis-associated proteins levels.
Results: We found that OPNpt20 exerts a robust pro-angiogenic effect in HUVECs, including proliferation, migration, and tube formation. OPNpt20 also induced blood vessel formation in a Matrigel plug assay in mice. However, a mutant peptide (OPNpt20-RAA), in which RGD was replaced by RAA, failed to activate all of pro-angiogenic processes, indicating that the RGD motif is required for its pro-angiogenic effect. In OPNpt20-treated HUVECs, PI3K/AKT signaling was activated. Moreover, blocking avb3 integrin by antibody or treating OPNpt20 after pre-incubating it with avb3 integrin suppressed OPNpt20-mediated pro-angiogenic function, indicating that OPNpt20 stimulates angiogenesis via avb3/PI3K/AKT signaling pathway in HUVECs. Pro-angiogenic function of OPNpt20 was further confirmed in the postischemic brain, wherein significant inductions of RECA-1 immunoreactivity as well as angiogenesis-associated proteins, such as, VEGF, MMP-9, and smooth muscle actin, were also observed in cortex penumbras of OPNpt20-administered animals.
Conclusion: Together these results demonstrate that RGD-containing OPN peptide has a robust pro-angiogenic effects and it might contribute to a robust neuroprotective effects in the postischemic brain.
982
BRAIN-0424
Non-Registered Abstracts
Non-Registered Abstracts
RELATIONSHIP BETWEEN MYELINATION AND CORTICAL FOLDING IN DEEP SULCAL LANDMARKS
J.M. Lee1 and HJ Yun1
1Department of Biomedical Engineering, Hanyang Univ., Seoul, Korea
Abstract
Objective: Sulcal pits, known as deep sulcal landmarks, are thought to be regions of cortical growth and first folded area under genetic control. Furthermore, sulcal pits have close relations to cytoarchitectonic areas and retain their identity during development. In neuroimaging studies, gray matter (GM) and white matter (WM) show age-related trajectory with myelin levels and neuronal density. Especially in GM development, cortical folding is dependent on tension of connected tracks in WM. Many researchers employ the diffusion parameters which are assessed for WM tracks and cortical thickness known as a quantitative measure of GM structure to proof the correlation between them. However, most previous studies have not concentrated on deep sulcal regions.
In this study, we investigate that brain morphological features are affected by diffusion parameters in deep sulcal landmarks. Furthermore, we examine age-related changes in cortical folding and WM integrity young healthy subjects.
Methods:
Image processing: The WM and GM cortical surfaces were extracted from structural MRIs using the Constrained Laplacian-Based Automated Segmentation with Proximities algorithm. The sulcal pits are identified by watershed algorithm on WM depth map. Cortical thickness, sulcal depth, absolute mean curvature and surface area were extracted from GM surfaces and regional averaged in sulcal pits. The mean diffusivity (MD) value is measured in diffusion images which are co-registered to their structural MRIs, and calculated in WM regions around sulcal pits with 5 mm distance threshold.
Statistical analysis: Linear effects of age on each morphology and diffusion features in deep sulcal regions are calculated for both hemispheres by general linear models (GLMs). To investigate the correlations between GM and WM parameters, we also employ GLMs regressing for effects of gender and age.
Results: The linear models with age are significant for MD (t = −5.16; p < 0.001) and absolute mean curvature (t = −2.62; p = 0.011). However, the MD and absolute mean curvature show a positive relationship trend (t = 1.81; p = 0.075) instead of significant relationship. Cortical thickness (t = 2.10; p = 0.039) and sulcal depth (t = 2.12; p = 0.038) correlate positively with MD, although the linear effects of age on them are not significant. Surface area is not any significant results in both GLMs.
Conclusion: We found age-related changes in MD and curvature which indicate myelination and deformation in deep sulcal regions. The results of the relationship between diffusion parameter and morphological features further demonstrate possibility that cortical growth in the first folded area could be associated with WM integrity.
983
BRAIN-0253
Non-Registered Abstracts
Non-Registered Abstracts
EFFECT OF A BROAD SPECIFICITY CHEMOKINE BINDING PROTEIN ON BRAIN LEUKOCYTE INFILTRATION AND INFARCT DEVELOPMENT
S. Lee1, HX Chu1, HA Kim1, NC Real2, S Sharif2, SB Fleming2, AA Mercer2, LM Wise2, GR Drummond1 and CG Sobey1
1Department of Pharmacology, Monash University, Clayton, Australia
2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
Abstract
Objectives: Expression of numerous chemokine-related genes is increased in the brain following ischemic stroke. Here, we tested whether post-stroke administration of a chemokine binding protein (CBP), derived from the parapoxvirus bovine papular stomatitis virus, might reduce infiltration of leukocytes into the brain and consequently limit infarct development.
Methods: The binding spectrum of the CBP was evaluated in chemokine ELISAs and binding affinity was determined using surface plasmon resonance. Focal stroke was induced in C57Bl/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion for 23 or 47 h. Mice were treated intravenously with either bovine serum albumin (BSA, 10 µg) or CBP (10 µg) at the commencement of reperfusion. At 24 or 48 h, we assessed plasma levels of the chemokines CCL2/MCP-1 and CXCL2/MIP-2, as well as neurological deficit, brain leukocyte infiltration, and infarct volume.
Results: The CBP interacted with a broad spectrum of CC, CXC and XC chemokines, and bound CCL2/MCP-1 and CXCL2/MIP-2 with high affinity (pM range). Stroke markedly increased plasma levels of CCL2/MCP-1 and CXCL2/MIP-2, as well as numbers of microglia and infiltrating leukocytes in the brain. Increases in plasma chemokines were blocked in mice treated with CBP, in which there was reduced neurological deficit, fewer brain-infiltrating leukocytes and ∼50% smaller infarcts at 24 h compared with BSA-treated mice. However, CBP treatment was no longer protective at 48 h.
Conclusions: Post-stroke administration of CBP can reduce plasma chemokine levels in association with temporary attenuation of brain inflammation and infarct volume development.
984
BRAIN-0751
Non-Registered Abstracts
Non-Registered Abstracts
CHARACTERIZATION OF CEREBRAL DAMAGE IN A MONKEY MODEL OF ALZHEIMER’S DISEASE INDUCED BY INTRACEREBROVENTRICULAR INJECTION OF STREPTOZOTOCIN
Y. Lee1, H Yeo1, C Jeon1, Y Jin1, K Jeong1, S Lee1 and K Chang1
1National Primate Research Center, Korea Research Institute of Bioscience & Biotechnology, Cheongju-si, Korea
Abstract
In line with recent findings showing Alzheimer’s disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-human primate models are very limited. In this study, we aimed to characterize the cerebral damage caused by icv-STZ in non-human primates; to achieve this, three cynomolgus monkeys (Macaca fascicularis) were administered four dosages of STZ (2 mg/kg) dissolved in artificial cerebrospinal fluid and another three controls were injected with only artificial cerebrospinal fluid at the cerebellomedullary cistern. In vivo neuroimaging was performed with clinical 3.0 T MRI, followed by quantitative analysis with FSL for evaluation of structural changes. Immunohistochemistry was performed to evaluate histopathology. We showed that icv-STZ caused severe ventricular enlargement and parenchymal atrophy accompanying accumulation of beta-amyloid and phosphorylated tau proteins in the parenchyma of the insula or temporal cortex. Hippocampal cell loss, disintegration of the neurovascular unit, neuroinflammation with microglial activation, and ependymal cell loss, which are observed in human aged or AD brain, also occurred. The findings suggest that the icv-STZ monkey model would be a valuable resource to study the mechanisms and consequences of a variety of pathologies such as ventriculomegaly and amyloidopathy. Furthermore, the study of icv-STZ monkeys could contribute to the development of treatments for age- or AD-associated pathologies.
985
BRAIN-0752
Non-Registered Abstracts
Non-Registered Abstracts
A BLOOD-BASED TRANSCRIPTIONAL PROFILING IN A NONHUMAN PRIMATE MODEL OF ALZHEIMER’S DISEASE INDUCED BY INTRACEREBROVENTRICULAR INJECTION OF STREPTOZOTOCIN
Y. Lee1, H Yeo1, C Jeon1, Y Jin1, K Jeong1, S Lee1 and K Chang1
1National Primate Research Center, Korea Research Institute of Bioscience & Biotechnology, Cheongju-si, Korea
Abstract
As nonhuman primates share significant genetic, anatomical, physiological, and behavioral traits with humans, they are critical experimental model to investigate human neurodegenerative disease including Alzheimer’s disease (AD). In line with recent findings showing AD as an insulin-resistant brain state, an animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD, showing AD-like features. However, the effect of icv-STZ on the blood-based transcriptional profiling has not been investigated in nonhuman primates. In this study, we performed a whole genome screen using oligonucleotide microarray analysis on bloods from icv-STZ-treated or normal control cynomolgus monkeys (Macaca fascicularis) as a pilot study. Blood samples for total RNA extraction were collected in PAXgene tubes, and gene expression analysis performed on the Agilent’s Rhesus Macaque Gene Expression Microarray. The PANTHER website was used to search for the biological significance. 2166 genes were up-regulated and 830 genes were down-regulated in the icv-STZ blood, compared with control (more than 2-fold, p < 0.05). In the up-regulated genes, 23 biological processes were significantly overrepresented (p < 0.05) in the signature: cellular process, cell communication, developmental process, multicellular organismal process, single-multicellular organism process, system process, system development, cell adhesion, biological adhesion, response to stimulus, immune system process, neurological system process, nervous system development, mesoderm development, ectoderm development, localization, cell-cell signaling, transport, response to external stimulus, synaptic transmission, cell-cell adhesion, angiogenesis, reproduction. On the other hand, in the down-regulated genes, only translation was significantly overrepresented (p < 0.01). Our findings implicate the systemic nature of gene dysregulation in icv-STZ monkey.
986
BRAIN-0880
Non-Registered Abstracts
Non-Registered Abstracts
INFLUENCE OF 3-METHYLXANTHINE DERIVATIVE ON THE MORPHOLOGICAL AND FUNCTIONAL CHARACTERISTICS OF NEURONS OF SENSORIMOTOR CORTEX OF RATS WITH EXPERIMENTAL INTRACEREBRAL HEMORRHAGE
I. Belenichev1, K Aleksandrova2, A Shkoda2, S Levich2 and S Nosach1
1Pharmacology and Medical Formulation, Zaporozhye State Medical University, Zaporozhye, Ukraine
2Biochemistry and Laboratory Diagnostics, Zaporozhye State Medical University, Zaporozhye, Ukraine
Abstract
The modern concept of neuroprotection during intracerebral hemorrhage includes sequential administration of primary and secondary neuroprotectors. In the article are represented results of in-depth study of a novel xanthine derivative – hydrazide of 1,3-dimethyl-8-N-benzylaminoхanthinyl-7-acetic acid (compound C-3), which previously showed high neuroprotective, antioxidant and energotropic activity.
The aim of the research was to study the effect of compound C-3 on morphofunctional parameters of neurons of the sensorimotor cortex of rats with experimental intracerebral hemorrhage.
We studied effect of compound C-3 on such morphofunctional parameters of neurons of IV-V layers of the sensorimotor cortex of rats with experimental intracerebral hemorrhage - neuronal density (number of cells per 1 mm2 area of slice of cerebral cortex), the cellular content in the IV-V layers of the cortex in percentage; area of bodies of neurons (mm2), RNA content in neurons.
Intracerebral hemorrhage was modeled in albino rats of both sexes weighing 140–160 g (90 animals) by injection into the region of the internal capsule and striatopallidal cores of the brain autologous blood, which was taken from the tail vein. Compound C-3 was injected at a dose of 100 mg/kg/day intragastrically as a suspension stabilized by Tween-80 during 4 or 18 days. As reference drugs were used mexidol and piracetam at doses of 100 mg/kg and 500 mg/kg, respectively.
It was shown that the course administration of hydrazide 1,3-dimethyl-8-N-benzylaminoхanthinyl-7-acetic acid (С-3) at dose 100 mg/kg intragastrically to rats with experimental intracerebral hemorrhage caused a significant neuroprotective effect. Neuroprotective action of compound C-3 was implemented in the acute period of еxperimental рathology and manifested in a positive influence on the morphological and functional parameters of neurons of IV-V layers of the sensorimotor cortex. a significant increase in neuronal density and an increase in RNA content in the neurons of both the 4th (the most pronounced effect) and on the 18th day after intracerebral hemorrhage. This fact indicates that the injection of the C-3 reduced neuronal damage and improved the processes of transcription and translation in the cells. The level of influence on the morphological and functional parameters of neurons in experimental intracerebral hemorrhage of novel xanthine derivative C-3 significantly superior on the 4th day of the experiment piracetam and mexidol, and on the 18th day - piracetam.
Thus, the neuroprotective effect of compound C-3, in contrast to the reference drugs, realized in the acute phase of experimental pathology and had a positive effect on the functional activity of neurons.
987
BRAIN-0938
Non-Registered Abstracts
Non-Registered Abstracts
COMPUTATIONAL FLUID DYNAMICS FOR FLOW ASSESSMENT IN DIGITAL SUBTRACTION ANGIOGRAPHY
C.Y. Hsu1, M Ghaffari1, A Alaraj2 and A Linninger1
1Bioengineering, University of Illinois at Chicago, Chicago, USA
2Neurosurgery, University of Illinois at Chicago, Chicago, USA
Abstract
Objectives: In this study, we introduce a novel inversion-based method to quantify blood flow from digital subtraction angiography intensity profiles. Neuro-interventional surgery is at the forefront of fast-response assessment of patients’ health. Unfortunately, cerebral blood flow cannot be reliably measured with digital subtraction angiography during intervention. We propose to combine image processing for patient-specific anatomical data, and computational modeling with flow physics for flow quantification in digital subtraction angiography. By providing flow quantification in digital subtraction angiography, we wish to facilitate clinical diagnosis for cerebral vascular diseases.
Methods: We processed 3D rotational angiography to create a network representation of the main cerebral arteries. We extracted from the 2D digital subtraction angiography the intensity profiles along the vessel centerlines. We feed the intensity into a fluid mechanic equations that allow us to infer blood flow based on equations of blood motion and dye convection. The automation of the procedure has several innovative elements. (1) The automatic image reconstruction of the arterial tree. (2) The fully automatic coregistration of intensity data with vascular segments in the simulation. (3) The dynamic generation of an inversion problem, the computation of the flow and the display of a flow map for all visible blood vessels for a specific patient.
Results: We collected medical images from six patients including 3D rotational angiography, 2D digital subtraction angiography, and quantitative magnetic resonance angiography for comparison. We show in six patients that the flow rates are as accurate as quantitative magnetic resonance angiography. We also validated the accuracy of the method using a 3D realistic blood flow phantom with known flow.
Conclusions: By combining image processing and computational modeling, we developed an algorithm that estimates volumetric flow rates from 2D digital subtraction angiography and 3D rotational angiography. Our algorithm provides neurosurgeons with quantitative flow measurements within an hour, which can be improved to minutes by incorporating parallel processing [1].
2D-DSA contrast agent intensity vs. time curves for selected vessels in the Circle of Willis (post-intervention, Patient 2). For each arterial point of interest (RICA, MCA, etc.), the red dots show the intensity values on the y-axis acquired from DSA for the first 5 seconds after bolus injection. The smooth black curve represents the best fit of the red dots using the inversion technique. The best fit solution also precisely determines the flow in all visible blood vessels.
Reference
Asano, S.; Maruyama, T.; Yamaguchi, Y. Performance comparison of FPGA, GPU and CPU in image processing. In International Conference on Field Programmable Logic and Applications, 2009. FPL 2009; 2009; pp. 126–131.
988
BRAIN-0939
Non-Registered Abstracts
Non-Registered Abstracts
HEMODYNAMIC SIMULATION OF THE PATIENT SPECIFIC CEREBRAL BLOOD FLOW TOWARDS A PERSONALIZED SURGICAL PLANNING FOR VASCULAR DISORDERS
M. Ghaffari1, CY Hsu1, A Alaraj2 and A Linninger2
1Bioengineering, University of Illinois at Chicago, Chicago, USA
2Neurosurgery, University of Illinois at Chicago, Chicago, USA
Abstract
Objectives: The aim of this work is to generate a patient-specific surgical planning tool for cerebrovascular disease. We performed patient-specific hemodynamic simulations in all main visible vessels to better assess normal and disease states of cerebral blood flow. Hemodynamic simulation of cerebral blood flow requires reconstruction of human angioarchitecture. We acquired patient-specific medical images and reconstructed an anatomically accurate blood flow network counting hundreds to thousands of vessels using an automatic mesh generation algorithm.
Methods: Magnetic resonance imaging was acquired for one healthy volunteer. A vessel filter was applied to suppress signals from other tissues and enhance the vessels (Fig. 1A). The filtered image was process to acquire centerlines and diameter information [1–2], as shown in Fig. 1B.
For hemodynamic simulations, we developed a parametric meshing algorithm to automatically generate surface and volumetric meshes for extracted centerline and radius information (Fig. 1C). Parametric meshes allow for a massive reduction in mesh size, while maintaining meshes quality especially close to the vessels wall where the wall shear stresses are highest. Parametric meshing allows us to control vessel lumen and wall thickness for accurate representation of cerebral angioarchitecture
We used phase contrast magnetic resonance imaging (pcMRI), guided by NOVA software (VasSol Inc., Chicago, IL) to quantify blood flow in large portions of the main cerebroarterial trees. The NOVA software was used for the determination of volumetric blood flow rates using planes perpendicular to the vessel axis (Fig. 1D-E). Based on the parametric meshes the hemodynamic simulations were carried out using ANSYS Fluent 15.0 (ANSYS Inc., Canonsburg, PA).
Results: The quantitative analysis blood flow rate showed good agreement between the simulation and NOVA results. Our 3D simulation of a complete Circle of Willis (CoW) demonstrates velocity field, pressure gradient, with a pulsatile blood flow (Fig. 1F). Dynamic contrast agent distribution for three time frames 0.25 s, 0.45 s, 0.65 s after injection of a contrast agent is shown in Fig. 1G
The simulation results demonstrate the use of our image processing, and meshing techniques with simulation to aid clinical diagnosis. The patient-specific simulations allow quantifying angiographic dye perfusion to illustrate the blood perfusion patterns in the normal subjects and patients with neurovascular diseases such as aneurysms, atherosclerotic and stroke.
Conclusion: These results are encouraging and point to the huge potential of patient-specific simulations to quantify hemodynamic of cerebral vessels to assist in making clinical decisions in surgery. This study can be used for personalized therapy for vascular disorders such as optimization of intracranial aneurysm clipping.
References
AntigaLPiccinelliMBottiLEne-IordacheBRemuzziASteinmanD A. An image-based modeling framework for patient specific computationla hemodynamics. Medical and Biological Engineering and computering2008; 46: 1097–1112.M. Ghaffari, C.Y. Hsu, A.A. Linninger, 2015, Automatic Reconstruction and Generation of Structured Hexahedral Mesh for Non-planar Bifurcations in Vascular Networks, Computer Aided Chemical Engineering, volume 37.
989
BRAIN-0133
Non-Registered Abstracts
Non-Registered Abstracts
MONITOR GENE THERAPY IN VIVO USING TARGET-GUIDED MRI: A PRECLINICAL PLATFORM
P. Liu1, YI Chen1 and J Wu2
1Radiology, Massachusetts General Hospital, Charlestown MA, USA
2Biomedical Science, Florida Atlantic University, Boca Raton FL, USA
Abstract
Objectives: Therapy usingexogenous gene has been used to treat neurological disorders. However, itsvalidation of delivery and expression depends on necropsy samples, which is notapplicable clinically. Such deficiency can be addressed using target-guidedmagnetic resonance imaging (MRI) in vivo.
Granulocytecolony-stimulating factor (G-CSF) is a cytokine that stimulates growth anddifferentiation of myeloid precursors. In addition, G-CSF has neuroprotectiveproperties in animal models of Parkinson disorder, stroke, Alzheimer dementiaand other neurodegenerative diseases. Protein therapy using G-CSF is attractivebecause G-CSF is well tolerated after systemic delivery and its receptor isexpressed in neurons. However, its plasma half-life is about 4 hours; moreover, there is potential for chronically elevating white blood cells during repeatedprotein delivery. One alternative is to administer human G-CSF (hG-CSF) encodedby a viral vector (gene therapy)–namely a replication deficientadeno-associated virus (AAV).
Our objectives are to(1) delivery hG-CSF cDNA in AAV-CMV vector, (2) direct monitor the expressionof G-CSF from AAV-CMV-hG-CSF in vivo and (3) neuroprotection in vivo usinghG-CSG-targeting magnetic resonance imaging (MRI) in living brains aftercerebral ischemia models by bilateral carotid artery occlusion (BCAO) ofC57black6 mice.
Methods: Brain damage was inducedusing bilateral carotid artery occlusion (BCAO) for 60 min in C57black6 mice. Wedelivered AAV-CMV-hG-CSF or AAV-CMV-GFP (placebo) to mice immediately after therelease of BCAO (4 × 109 fpu in 2 ul, eye drops) and at 1, 7, and 14days thereafter. We made sODN with antisense sequence for hG-CSF mRNA. Our sODNtargets hG-CSF mRNA, but not rodent G-CSF mRNA. We linked the sODN to superparamagnetic ironoxide nanoparticles (SPION, a T2 susceptibility agent, 4 mg Fe per kg) orgadolinium (1 ug), all delivered by non-invasive intraperitoneal injection threedays after the last AAV-CMV-hG-CSF vector application. We acquired MRI 16 hourslater.
Results: The survival rateof C57black6 mice by 60 min of BCAO is 5 out of 38 mice in two experiments. Genetherapy using AAV-CMV-hG-CSF improves survival rate (5 of 6 in two trails). Micetreated with AAV-CMV-hG-CSF after BCAO show less brain damage by ventriculomegalyusing MRI, and corner turn test shows improved bilateral turns from unilateralturns. We observed expression of hG-CSF mRNA in vivo using SPION-hG-CSF and targetguided MRI. The region of hG-CSF expression was validated using anti-h-G-CSFIgG and expression of neural progenitor cells in necropsy samples. Brain repairwas absent in the placebo group with BCAO and AAV-CMV-GFP.
Conclusion: We demonstratedgene tracking using hG-CSF-targeting MRI in vivo. The significance of thisproject is in correlating gene delivery and the accompanied neuroprotection. This is the first step in translating longitudinal MRI of brain repair withoutbiopsy during therapy throughout the life time of patients afflicted withneurodegenerative disorders.
Acknowledgement: Supported by the Boston Area Diabetes EndocrinologyResearch Center [P30DK057521-14 (J Avruch)], DA029889 and EB013768 (PKL). TheMRI system was funded in part by NIH (S10RR025563) to the Martinos Center forBiomedical Imaging, MGH.
990
BRAIN-0025
Non-Registered Abstracts
Non-Registered Abstracts
TRAUMATIC EXPERIENCE AND MENTAL EFFECTS AMONG RWANDAN YOUTHS, 17 YEARS AFTER THE GENOCIDE
L. Lugema1, I Mogren2, J Ntaganira3 and G Krantz4
1Community Health, College of medicine and Health Sciences - School of Public Health, kigali, Rwanda
2Clinical Sciences Obstetrics and Gynecology, Umeå University., Umeå, Sweden
3Biostatistics and Epidemiology, College of medicine and Health Sciences - School of Public Health, kigali, Rwanda
4Public Health and Community medicine The Sahlgrenska Academy, Gothenburg University Public Health and Community medicine The Sahlgrenska Academy, Gothenburg, Sweden
Abstract
Background: Common mental disorders (CMD) contribute toapproximately 14% of the global burden of disease. Despite this CMDs have failed to attract the attentionof researchers and planners in low and middle income countries (LMCs) andsubsequently there is little detection and treatment of CMDs. This studyinvestigated the mental health effects associated with trauma exposure inRwanda during the 1994 genocide period and over the life time in Rwandan menand women, aged 20–35 years.
Methods: This cross-sectional population-based study was conducted among 440 menand 477 women, residing in the Southern province of Rwanda. The data collectionincluded individual interviewing followed by a structured questionnaire. Prevalencerates were calculated and multivariable logistic regression was employed forrisk factor analyses of common mental disorders with traumatic exposure as themain risk factor of interest.
Results: Women to ahigher extent than men suffered from major depressive episodes (MDE), suicide risk, post-traumatic stress syndrome (PTSD) and generalized anxiety disorder (GAD). MDE current was twice as prevalent in women as men. Traumatic episodesexperienced in the genocide period severely affected men's current mental healthstatus with OR 3.35 (CI 95% 1.64–6.84) for MDE past and OR 2.36 (95% CI 1.23–4.54) for suicide risk. Women's mental health was also affected by trauma experiencedin the genocide period but to a higher extent by similar trauma experienced inthe life time with OR 2.16 (95% CI 1.03–4.53) for suicide risk and OR 3.05 (95%CI 1.56–5.93) for GAD, taking spousal physical/sexual violence intoconsideration.
Conclusion: Impact of the genocide is still evident in today'speoples living circumstances. It has made a huge contribution to CMDs among Rwandan youths.
991
BRAIN-0704
Non-Registered Abstracts
Non-Registered Abstracts
GALECTIN-1 IS NEUROPROTECTIVE AND REVERSES METHAMPHETAMINE INDUCED BLOOD BRAIN BARRIER BREAKDOWN
NU Parikh1, S. Mahajan1, R Aalinkeel1, JL Reynolds1, BN Nair1, DE Sykes1, MJ Mammen1 and SA Schwartz1
1MEDICINE, SUNY at Buffalo, Buffalo, USA
Abstract
Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain-barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin-1 expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Treatment with 50 nM Meth treatment decreased Claudin-3 gene expression by 37% (p.
992
BRAIN-0916
Non-Registered Abstracts
Non-Registered Abstracts
DEEP VEIN THROMBOSIS IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURIES
P. Mendez1, A Chavez1, L Avila1 and A Seifi1
1Neurosurgery, UTHSCSA, San Antonio, USA
Abstract
Objectives: Deep venous thrombosis (DVT), often prodromal for pulmonary embolism, is known to cause significant morbidity and mortality.1 The use of postoperative chemoprophylaxis is still controversial among clinicians who care for severe traumatic brain injury patients due to concern of intracranial hemorrhage (ICH) and its pernicious effects. In the present study, we evaluated the incidence of DVT in severe traumatic brain injury (TBI), as well as the impact of chemoprophylaxis on development of DVT.
Methods: We conducted a retrospective case control study with patients admitted to University Hospital neurosurgical ICU in San Antonio, Texas from 2011–2013. Severe TBI was defined as patients who required intracranial pressure monitoring within 48 hours of admission. Patients who were less than 18 years of age, DVT on admission, pre-existing filter, pregnancy, chronic anticoagulation, and death within 72 hours after TBI were excluded.
Demographic data, etiology of TBI, complications, hospital length of stay (LOS), start date of chemoprophylaxis were gathered. Progression of ICH was defined as lesion expansion or development of a new ICH as documented by radiologist report on a repeat CT scan. Fisher’s exact test was utilized to determine incidence and mortality of DVT with and without chemoprophylaxis. The Mann-Whitney U test was utilized to determine hospital LOS.
Results: There were 396 qualifying records, 155 records entered the study group after exclusion criteria. The cohort was mostly composed of white (71.6%), male (76.8%) with a median age of 41. The majority types of TBIs were subdural hemorrhage (62.6%) & subarachnoid hemorrhage (60%).
A total of 122 patients received chemoprophylaxis, the average number of days post admission to begin prophylaxis being 5.04 ± 3.95. The mean number of days post stable head CT being 6.69. Meaning some patients received chemoprophylaxis prior to stable CT. The incidence of DVT was 12.26% and PE 2.58%. We found 30.3% of patients who did not receive chemoprophylaxis developed a DVT vs. 7.38% of patients who received chemoprophylaxis developed a DVT. See Figure 1.
We observed 9.35 days longer LOS in those who developed a DVT, and did not receive chemoprophylaxis. Our study mortality rate was 18%. The incidence of ICH progression after chemoprophylaxis was 7.74%.
Conclusions: Our data suggests a lower incidence of DVT in patients who received chemoprophylaxis and longer hospital LOS than the group did not. We found improved mortality in patients who received chemoprophylaxis at any point of their hospital stay. Thus, consider starting chemoprophylaxis to reduce patient complications of DVT, hospital length of stay, and hospital costs. Additional larger prospective studies should be undertaken to confirm the best time to begin chemoprophylaxis in severe TBI patients.
Reference
Farooqui A, Hiser B, Barnes S, et al: Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial traumatic brain injury. Journal of Neurosurgery 2013; 1.
993
BRAIN-0714
Non-Registered Abstracts
Non-Registered Abstracts
CEREBRAL BLOOD CIRCULATION AT EXPERIMENTAL CAROTID-JUGULAR FISTULA
V. Musienko1
1Department of pathophysiology, Lugansk medical university, Lugansk, Russia
Abstract
Objectives: Cerebral circulatorydisorders at extracranial arteriovenous fistulas and aneurysms arethe main pathogenic factor of the brain damage and therefore requiredetailed study.
Methods: Carotid-jugular fistula was modeled on 40dogs. Physiological and morphological methods of investigation were used.
Results: Morphological changes of the cerebral venoussystem within acute period were characteristic for venous plethora. Diameter ofthe superficial and intracerebral branches of the cerebral arteries wasincreased. Total expansion of the cerebral microcirculatory bed was found.
Further reconstruction was accompanied by formation ofthe vascular system of arteriovenous fistula, collateralarterial circulation and collateral venous one. Collateral arterial cerebralcirculation included dilated carotid and vertebral arteries, extracranialcommunications between them, brain arterial circle, cerebral arteries and theirintracerebral branches and superficial arterial net with anastomoses here. The waysof collateral venous outflow included transformed superficial venous networksof the brain, dural sinuses, additional ways of venous outflow from skullcavity.
Drainage system of arteriovenous fistula includedextracranial veins, dural transversal sinuses and their connections withvertebral venous pool providing mainly extracranial redistribution of theshunted blood. This system developed expansively in result of involving ofincreasing number of arterial branches in blood shunting and also veins intofistula drainage system.
Conclusion: Extracranial arteriovenous fistulas resultin noncompensative disturbances of the cerebral blood circulation. Involving intact arteries, including intracranial ones, in supply of the arteriovenous fistula accompanies by “robbery” ofthe cerebral arterial circulation. Increased disproportion of the arterialinflow ways to the brain and the ways of collateral venous outflow formspredispositions for relative arterial stenosis syndrome. Cerebralmicrocirculatory bed transformation forms the ways for intracerebralarteriovenous blood shunting and pathological acceleration (“centralizations”) of the cerebral blood flow.
994
BRAIN-0243
Non-Registered Abstracts
Non-Registered Abstracts
PLACEBO EFFECT OF AESTHETIC PACKAGING DESIGN IN TREATMENT OF HEADACHES
Z. OUAZZANI TOUHAMI1, A CHAKOR2, HO EL MALKI3 and A BENOMAR4
1Medico-social Department, Hight Institut of Nursing and Health Techniques, RABAT, Morocco
2Management Department, Faculty of Juridical Economic and Social Sciences University Mohammed Vth, RABAT, Morocco
3Anatomy Department, Medical School University Mohammed Vth, RABAT, Morocco
4Neurology Department, Abulkasis International University of Health Sciences, RABAT, Morocco
Abstract
Introduction: Packaging is an extrinsic part of the product. Many studies examine the influence of packaging design on consumer behavior. Our study tests the influence of pharmaceutical packaging design on preference and satisfaction.
Methods: The effect of aesthetic packaging design of two brands of analgesic used to treat headaches was studied in a sample of women and men when they suffer from headaches. We first conducted a pretest to identify two brand’s packaging: the most attractive and the least attractive. The two brands of analgesic contain an active formulation. The sample was randomly into two groups in which subjects received the brand to have an attractive packaging design (Group 1), or that which is have an unattractive packaging design (Group 2). Data were collected by the subjects themselves when they suffered from headaches through a numerical scale of pain assessment. Subjects evaluated their pain before taking an effervescent tablet 500 mg, then 20 min, 2 h and 4 h after taking it.
Results: The two groups have respectively at the evaluation times t0 = 5,96; t1 = 3,83; t2 = 2,38; t3 = 1,85 for the Group 1and t0 = 5,86; t1 = 4,3; t2 = 2,19; t3 = 1,05 for the Group 2.
We found no significant differences (p > 0,05, p = 0,736) between the potency of the attractive brand packaging analgesic and the unattractive one.
Conclusion: The findings showed that pharmaceutical packaging has no additional marketing placebo effect. Our results suggest that an attractive brand of analgesic has the same potency than an unattractive brand in relieving headaches.
995
BRAIN-0059
Non-Registered Abstracts
Non-Registered Abstracts
BLOOD–BRAIN BARRIER DYSFUNCTION IN PATIENTS WITH CEREBRAL MICROBLEEDS
T. Poliakova1, O Levin1, N Trusova1, P Hermann2, M Schmitz2 and I Zerr2
1neurology, Russian Medical Academy of Postgraduate Education, Moscow, Russia
2neurology, Nationales Referenzzentrum für TSE Klinik für Neurologie Universitätsmedizin Göttingen, Gottingen, Germany
Abstract
Background: We hypothesize that cerebral microbleeds (CMB) might be associated with endothelial dysfunction and blood–brain barrier (BBB) damage in patients with different neuropsychological MCI (mild cognitive impairment) profile. Both molecular biomarkers in the CSF and imaging techniques are suggested to be useful to identify AD and VaD at early stages. CMB are small rounded hypointense lesions found with gradient-echo (GRE) T2*-weighted or SWI of MRI sequences and are characterized histologically by the presence of haemosiderin deposits around small blood vessels with a diameter < 200 mm.
Methods: MCI patients were diagnosed as following: amnestic with CMB (n = 28) and without CMB (n = 33), non-amnestic with CMB (n = 33) and without CMB (n = 42). We analyzed CSF profiles (Aβ42, 40, tau, Ptau, Aß1-40/42, QAlb, cytokines), ApoE genotype and cognitive decline in MCI patients with respect to CMB load and profile in MRI. MRI was performed at 3.0 Tesla scanner using a susceptibility-weighted protocol. Neuropsychological assessment comprised MMSE, MoCA, ACE-R, CAMCOG (part 3).
Results: Sixty-one patients (45%) with a diagnosis of MCI had at least 1 CMB. Most of them were observed in amnestic MCI (67%). No significant differences between the groups stratified by CMB presence were found for Aβ42, 40, tau, Ptau and cytokines, but the ratio of Aß1-40/42 in non-amnestic MCI patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). We found four patients clinically diagnosed as a non-amnestic MCI with reduction Aβ-amyloid Q-coefficient (0.46; 0.40; 0.58; 0.67) as well as multiple cortical MBs (11;21;6;15). A relevant difference in albumin ratio as an indicator of the (BBB)- QAlb- was observed between groups with and without CMB (picture 1). The regression results demonstrated that age, WMHs score and albumin ratio were important predictors of CMBs presence (β = −0,258, p = 0,029, R2 = −0,093; β = 0,365, p = 0,036, R2 = 0,093; β = 0,158, p = 0,077, R2 = 0,027; β = 0,103, p = 0,036, R2 = 0,043; respectively).
Conclusions: Our data revealed that patients with CMB have more features of BBB dysfunction, which is demonstrated by CSF albumin ratio. Cases of subcortical CMB in non-amnestic MCI patients and increase Q-albumin in CSF might indicate VaD. It might be associated with the progression of ischemic vascular lesions (Wallin A. 1990). Many authors explain the prevalence of CMB largest number of vascular risk factors, inflammatory and BBB disturbance (Charidimou A. Werring DJ. 2014, Miwa K 2014). But number of studies concerning inflammation and BBB disturbance in CMB is currently very small. Previous study is provided no evidence for P-glycoprotein dysfunction, which indicated about decrease BBB disturbance in AD with CMB (Danielle ME van Assema, 2012). It might indicate that amyloid in cerebrovascular and neurodegenerative diseases are different. A β42 is retained in cerebrovascular of AD patients with CMB, while in contrast, VaD patients may possibly drain amyloid (Goos 2012). Further studies are needed to explain the potential link between BBB dysfunction and CMB.
996
BRAIN-0125
Non-Registered Abstracts
Non-Registered Abstracts
FORCED LIMB-USE ENHANCES BRAIN PLASTICITY THROUGH THE CAMP/PKA/CREB SIGNAL TRANSDUCTION PATHWAY AFTER STROKE IN ADULT RATS
H. Qu1 and C Zhao1
1Neurology, The first hospital of China Medical University, Shenyang, China
Abstract
Purpose: The mechanism underlying forced limb-use -induced structural plasticity remains to be studied. We examined whether the cyclic adenosine monophosphate (cAMP)–mediated signal transduction pathway was involved in brain plasticity and promoted behavioral recovery induced by forced limb-use after stroke.
Methods: Adult rats were divided into a sham group, an ischemia group, an ischemia group with forced limb-use, and an ischemia group with forced limb-use and infusion of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89). Forced limb-use began on post-stroke day 7. Biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on post-stroke day 14. Behavioral recovery was evaluated on post-stroke days 29 to 32, and the levels of cAMP, PKA C-α, phosphorylated CREB (pCREB), synaptophysin, PSD-95, BDA, and BrdU/NeuN were measured.
Results: The number of midline-crossing axons and the expression levels of synaptophysin and PSD-95 were increased after forced limb-use. Forced limb-use enhanced the survival of the newborn neurons and increased the levels of cAMP, PKA C-α and pCREB. These were significantly suppressed by H89. Behavioral performance improved with forced limb-use and was reversed with H89.
Conclusions: Enhanced structural plasticity and the behavioral recovery promoted by post-stroke forced limb-use are suggested to be mediated through the cAMP/PKA/CREB signal transduction pathway.
997
BRAIN-0033
Non-Registered Abstracts
Non-Registered Abstracts
NEUROPROTECTIVE EFFECT OF HYDROXYSAFFLOR YELLOW A AGAINST ISCHEMIA-REPERFUSION INJURY BY INHIBITING MITOCHONDRIAL PERMEABILITY TRANSITION PORE OPENING
S. Ramagiri1 and T Rajeev1
1Pharmacy, Birla Institue of Technology and Sciences, pilani, India
Abstract
Aim: The present study was designed to investigate the neuroprotective effects of hydroxy safflor yellow A (HSYA), an active ingredients of the Chinese herb Carthamus tinctorius L, and its molecular mechanisms against cerebral-ischemia reperfusion injury.
Methods: Cerebral ischemia reperfusion (I/R) injury was induced by middle cerebral artery occlusion (MCAO) for 30 min in Wistar male rats followed by 24 hrs reperfusion. Cerebral blood flow (CBF) was monitored by Laser-Doppler Perfusion and Temperature Monitor (moor VMF – LDF2, UK) using a flexible probe over the skull.
Key findings: I/R injury resulted severe deficits in cognition, sensorimotor and skilled motor functions, as assessed by neurological scoring, rotarod, photoactometer and Y maze. Moreover, it also resulted in elevated oxidative stress and Tumor Necrosis Factor (TNF- α) levels along with higher infarct size. HSYA treatment (8 mg/kg, i.v.) attenuated infract size, oxidative stress, neuro-inflammation along with improvement in motor and cognitive performance. However, administration of carboxyatractyloside (1 mg/kg, i.p.), an opener of mPTP, attenuated the protective effect of HSYA against cerebral I/R-injury.
Conclusion: Thus based on above observations, it may be suggested that HSYA possess neuro-protective effects possibly mediated via mPTP closing during reperfusion. Hence, HSYA can be considered a promising approach against cerebral ischemic reperfusion injury.
998
BRAIN-0044
Non-Registered Abstracts
Non-Registered Abstracts
MICROGLIAL INHIBITORY EFFECT OF GINSENG AMELIORATES COGNITIVE DEFICITS AND NEUROINFLAMMATION FOLLOWING TRAUMATIC HEAD INJURY IN RATS
P. Rinwa1, H Dhar1 and A Kumar1
1University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
Abstract
Traumatic brain injury produces several neuropathological alterations some of them are analogous to patients suffering from memory disorders. Role of neuroinflammation and oxidative stress has been suggested in the pathophysiology of brain injury induced-cognitive dysfunction. Therefore, the present study was designed to explore the possible role of ginseng and its interaction with minocycline (microglial inhibitor) against experimental brain trauma induced behavioral, biochemical and molecular alterations. Wistar rats were exposed to brain traumatic injury using weight-drop method. Following injury and a post-injury rehabilitation period of two weeks, animals were administered vehicle/drugs for another two weeks. Brain injury caused significant memory impairment in Morris water maze task as evident from increase in escape latency and total distance travelled to reach the hidden platform. This was followed by a significant decrease in time spent in target quadrant and frequency of appearance in target quadrant. Further, there was a significant increase in oxidative stress markers, neuroinflammation (Tissue Necrosis Factor-alpha and Interlukins-6) and acetylcholinesterase levels in both cortex and hippocampal regions of traumatized rat brain. Ginseng (100 and 200 mg/kg) and minocycline (50 mg/kg) treatment for two weeks significantly attenuated all these behavioral, biochemical and molecular alterations. Further, combination of sub effective doses of ginseng (50 and 100 mg/kg) and minocycline (25 mg/kg) potentiated their protective effects which was significant as compared to their effects alone. The results of the present study suggest that the therapeutic effects of ginseng might involve inhibition of microglial pathway against head trauma-induced cognitive impairment and neuroinflammation in rats.
999
BRAIN-0421
Non-Registered Abstracts
Non-Registered Abstracts
IMPACT OF ANEMIA ON OUTCOME IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY
M. Rodriguez1, A Ottesen1, K Carr2 and A Seifi2
1School of Medicine, University of Texas Health Science Center, San Antonio, USA
2Department of Neurosurgery, University of Texas Health Science Center, San Antonio, USA
Abstract
Objectives: The blood transfusion threshold for severe traumatic brain injury (TBI) patients has been a subject of much discussion. However, no consensus has been reached on the most beneficial transfusion threshold. We sought to further examining the impact of various hemoglobin (Hgb) threshold levels on outcomes in severe TBI patients.
Methods: We reviewed the records of patients admitted with severe TBI to University Hospital in San Antonio, Texas from 2011 to 2013. Severe TBI was defined as patients with TBI who required intracranial pressure monitoring within 48 hours of admission. Patients who were less than 18 years of age, pregnant, non-traumatic brain injuries, expired within 72 hours of admission, or received an operating room procedure for a non-TBI injury or a blood transfusion within 24 hours of admission were excluded.
Demographic data, the lowest Hgb level, and transfusion status were queried. The outcome measures were mortality, change in Glasgow Coma Scale (GCS) score, hospital length of stay (LOS), and intensive care unit length of stay (ICU LOS). Fisher’s exact test was utilized to compare the outcomes in the transfused and non-transfused groups using four different Hgb thresholds: 7, 8, 9, and 10 g/dL.
Results: During the study period, there were 407 qualifying records. After exclusion criteria were applied, 89 patients were enrolled in the study. The median age of cohort was 45, of which 82% were male and 56% received transfusions. The mortality rate of the cohort was 17%.
A Hgb greater than 8 g/dL was associated with a shorter ICU LOS [11 vs 15 days, p = 0.02] and a shorter hospital LOS [17 vs 32 days, p = 0.01]. (See Figure 1). We found no association between Hgb level and improvement in GCS. Of patients with Hgb less than 8 g/dL who were transfused, 8.5% died. Whereas, the mortality rate for those not transfused was 35.7% (p = 0.01).
Conclusions: Our data suggests that, in severe TBI patients, maintaining Hgb over 8 g/dL may shorten ICU and hospital lengths of stay. Although our data supports that liberal transfusion strategies do not positively impact measured outcomes in patients with severe TBI, it did suggest an association between blood transfusions and decreased mortality rates for patients with Hgb levels less than 8 g/dL. Additional prospective studies should be undertaken to determine the best transfusion threshold for severe TBI patients.
References
George M, et al. “Aggressive red blood cell transfusion: no association with improved outcomes for victims of isolated traumatic brain injury.” (2008) 8:337–343.RobertsDZygunD. “Anemia, red blood cell transfusion, and outcomes after severe traumatic brain injury”. Critical Care2012; 16: 154–154.SekhonM. “Association of hemoglobin concentration and mortality in critically ill patients with severe brain injury”. Critical Care2012; 16: R128–R128.WarnerM. “Transfusions and long-term functional outcomes in traumatic brain injury”. J. Neurosurg2010; 113: 539–546.
1000
BRAIN-0519
Non-Registered Abstracts
Non-Registered Abstracts
MICRORNAS (MIRNA), LET-7/MIR-98, DECREASE INFLAMMATION AND IMPROVE TIGHTNESS OF THE BLOOD BRAIN BARRIER (BBB)
S. Rom1, H Dykstra1, V Zuluaga-Ramirez1, N Reichenbach1 and Y Persidsky1
1Pathology, Temple University School of Medicine, Philadelphia, USA
Abstract
Objectives: Diseases of the central nervous system (CNS) cause a significant challenge, but regardless of their multiplicity, they share many universal features and mechanisms. For example, endothelial dysfunction is perhaps the earliest event in the initiation of vascular disease, caused by inflammation due to stroke, atherosclerosis, trauma or brain infection1. Increased blood-brain barrier (BBB) permeability represents a hallmark of CNS inflammation that occurs in variety of neuropathological conditions. Microvasculature endothelial cells are very active participants and regulators of inflammatory processes at a site of inflammation. Immune mediators and engagement of primary human microvascular endothelial cells (BMVEC) with leukocytes contribute to BBB impairment during neuroinflammation. Glycogen synthase kinase (GSK)-3b has been implicated as a key regulator of the inflammatory response. The anti-inflammatory effects of GSK3b inhibition have been shown in vitro and in several in vivo models of acute and chronic inflammation2,3. Recently, miRNAs have emerged as a class of gene expression regulators. The relationship between inflammation and miRNA expression remains largely unexplored.
Methods: We used microarray technology (miR Base version 16 screening of 1212 miRNAs) to identify miRNAs induced in human primary BMVEC after exposure to the pro-inflammatory cytokine, TNFa, with or without a GSK3b inhibitor. Selected miRNAs were overexpressed in BMVEC, an in vitro BBB model, and in an in vivo model. All animal studies were approval by the Institutional Animal Care and Use Committee and the animal care and handling were in accord with National Institutes of Health guidelines.
Results: miRNA array showed that 123 microRNAs were downregulated (1-fold) in cells treated with TNFa/GSK3b inhibitor. 14 miRNAs were common to the two groups. Among the highly modified miRNAs, let-7 and miR-98, were predicted by a bioinformatics approach to target several inflammatory molecules such as VCAM-1, CD99, L1CAM, IL8, IL6, CXCL1 and IP-10. Overexpression of let-7 and miR-98 in BMVEC decreased leukocyte adhesion to and migration across BMVEC monolayers and improved transendothelial resistance (TEER). Pretreatment of mice with let-7/miR-98 diminished leukocyte adhesion to and migration across BBB in vivo, and led to a reduction in BBB leakiness.
Conclusions: Overexpression of let-7 and miR-98 in endothelium reduced expression of selected cytokines and improved BBB function both in vitro and in vivo. In this work we explored use of GSK3b-regulated miRNAs as therapeutic tools to prevent deleterious effects of endothelial dysfunction on neuroinflammation.
References
FaraciFM. Protecting against vascular disease in brain. Am J Physiol Heart Circ Physiol2011; 300(5): H1566–82.Woodgett JR, Ohashi PS. GSK3: an in-Toll-erant protein kinase? Nat Immunol 2005; 6(8): 751–2.RamirezSHFanSDykstraHRomSMercerAReichenbachNL. Inhibition of Glycogen Synthase Kinase 3beta Promotes Tight Junction Stability in Brain Endothelial Cells by Half-Life Extension of Occludin and Claudin-5. PLoS One2013; 8(2): e55972–e55972.
1001
BRAIN-0489
Non-Registered Abstracts
Non-Registered Abstracts
IL-1A ENHANCES ANGIOGENIC NEUROREPAIR AFTER EXPERIMENTAL ISCHEMIC STROKE
K Salmeron1 and E Pinteaux2, G. Bix1
1Sanders Brown Center on Aging, University of Kentucky, Lexington, USA
2Department of Life Sciences, University of Manchester, Manchester, United Kingdom
Abstract
Objective: Stroke is a major cause of death and disability worldwide. Unfortunately, all clinical trials that have targeted the primary cerebral ischemia (CI) injury mechanisms of oxidative stress and excitotoxicity have failed. However, CI also induces a potent local inflammatory response that leads to damage in the ischemic penumbra but may also, less acutely, initiate and sustain post-stroke repair processes such as angiogenesis. We hypothesize that the pro-inflammatory cytokine IL-1α promotes angiogenesis after stroke via generation of pro-angiogenic perlecan laminin globular domain 3 (LG3) protein fragments from the brain extracellular matrix. This is based on our previous observations that LG3 is rapidly and persistently generated after CI in vivo, and that IL-1α causes cells of the neuromuscular unit to generate LG3 in vitro. Importantly, the potential role of IL-1α in brain angiogenesis has not been previously studied.
Methods: Adult male C57/Bl6 mice underwent distal transient middle cerebral artery occlusion (MCAO) for 1 hour. IL-1α levels were measured at PSD 3, 7 and 21. In vitro angiogenesis assays were performed in 12, 24, and 96 well plates with brain endothelial cells isolated from C57/Bl6 mice. Cell lysates were obtained to determine levels of VCAM-1, ICAM-1 and iNOS by qPCR and Western Blot respectively. MTS Assays were performed using a spectrophotometric plate reader. Migration experiments were done using Scratch/Wound and Boyden Chamber modalities. Finally, capillary morphogenesis assays were performed on growth factor reduced Matrigel.
Results: IL-1α activates primary endothelial cells (BECs) in vitro and significantly enhances several stages of BEC angiogenesis including proliferation, migration and capillary tube-like structure morphogenesis. IL-1α levels are chronically (21 days) elevated (measured by qPCR and ELISA) suggesting that IL-1α persists beyond the acute stroke phase to affect post-stroke angiogenic repair. Finally, IL-1α deficient mice have diminished post-stroke penumbral angiogenesis.
Conclusions: Our results collectively suggest that inflammatory mediators such as IL-1α, in addition to their acute deleterious effects, may play an important and previously unrecognized role in post-stroke angiogenic neurorepair that could be therapeutically exploited.
1002
BRAIN-0023
Non-Registered Abstracts
Non-Registered Abstracts
THE CORRELATION BETWEEN BULIMIA NERVOSA AND BIPOLAR PATIENTS REFERRED TO PSYCHIATRY CLINIC. KERMANSHAH, IRAN, 2012–2014
J. Shakeri1, H Shakeri1, F Arman1 and M Shakeri1
1Psychiatry, Kermanshah University of Medical Sciences, Kermanshah, Iran
Abstract
Introduction: Bulimia nervosa(BN) is an eating disorder characterized by binge eating large amounts of food and then purge. Although the incidence rate is still a matter of debate, the prevalence rate has been increasing all over the world.
BMD is a mental disorder characterized by abnormal and elated or irritable mood possibly with depressive episodes at times.
Objective: The aim of this study was to investigate any possible relationship between bipolar disorder and Bulimia nervosa in order to improve the standard of living among these patients.
Methods: 130 known cases of BMD were interviewed and the data was gathered with demographic and Bulimia self-report questionnaire. The data was analyzed with SPSS 21 software.
Results: Of 130 patients, 85 patients (65.38%) were female and 45 patients (34.61%) were male. Most prevalent age group was between 20–40 years (M = 28.7, S.D = 3.4). The mean BMI of patients was 27.82 kg/m2 with SD equal to 9.54. 72 (55.38%) of patients were single while 58 (44.61%) were married. 76 patients (58.46%) lived in city and 54 of them (41.53%) lived in countryside. 80 patients (61.53%) had high school education or below and 50 (38.46%) had high school diploma or higher.
45 patients were diagnosed with bulimia. 40 patients were female with an incidence rate of 88.88% and 12.22% between male.32 patients had history of drug abuse and 5 of them had a history of suicide attempt. We compared these results in these two groups of patients. Patients with BMD had a significantly higher prevalence of bulimia. Patients with co-morbidity of bulimia and BMD had double suicide attempts and their drug dependency was 3 times more than BMD without bulimia.
Discussion: Although prevalence of bulimia in normal population maybe higher than our current knowledge due to the nature of the disorder which tends to go under-recognized, our study showed that there is significantly higher incidence of bulimia in bipolar patients. We suggest that:
1. The possibility of co-morbidity of BMD and Bulimia should be considered in resistant cases of both disorders.
2. Clinician should pay close attention to possible drug and non-drug interactions of treatment of both diseases.
1003
BRAIN-0131
Non-Registered Abstracts
Non-Registered Abstracts
NON-INVASIVE BRAIN AND KIDNEY COOLING IN SEVERE MULTISYSTEM BRAIN INJURY COMPLICATED BY SEPTIC SHOCK
V Avakov1 and I. Shakhova1
1Anaesthesiology Resuscitation and Intensive Care, Tashkent MAdical Academy, Tashkent, Uzbekistan
Abstract
Background. The worldwide burden of sepsis is high and is increasing (Stehr SN et al., 2013). Brain dysfunction is a severe complication of sepsis with an incidence ranging from 9% to 71% that is associated with increased morbidity and mortality (Siami S et al., 2008). Our understanding of sepsis-associated acute kidney injury pathophysiology is shifting from renal vasoconstriction, ischemia, and acute tubular necrosis to heterogeneous vasodilation, hyperemia, and acute tubular apoptosis (Koçkara A et al., 2013). Regarding pathogenesis, rates of morbidity and mortality are aimed to be reduced through the new methods of therapy that have been studied (Koçkara A et al., 2013). Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients (Adam N et al., 2013).
The aim of our study was to optimize prevention and treatment of acute kidney injury and toxic encephalopathy in patients with severe traumatic brain injury combined with an acute surgical abdominal pathology and complicated by septic shock.
Materials and Methods. During the period from 2011 to 2014 18 patients were admitted to our hospital urgently because of injury due to accidents, falls, fights. All patients were subjected to emergency surgery - midline laparotomy (ML), 10 of them (55%) cases of simultaneous operations: removal of intracranial hematoma (hydroma) with ML. ML accompanied nephrectomy (3 patients), nephrectomy with splenectomy (3 patients), nephrectomy with resection of the liver (2), splenectomy (3), resection of liver and intestine (4) and bowel resection (3). After ML laparostomy set (Fig. 1) to the disappearance of signs of sepsis.
Fig.1. Photo of patient with severe multisystem traumatic brain and abdominal injury complicated by septic shock (Day 83 in the ICU).
Fig.2. Method of brain cooling (schematic view)
3–5 days in 12 patients showed signs of toxic encephalopathy, 5–8 days - liver failure (6 patients), 7–11 - renal failure (7), 6–12 - septic shock (18), 8 - refractory septic shock, 18 - hyperthermic syndrome. Malignant fever was observed in 9 patients.
Due to the above, for 2–4 days in all patients on the basic therapy with prophylactic or therapeutic purposes began brain (Fig. 2) and kidney (Fig. 3) cooling in accordance with the method developed by us.
Method of kidney cooling (schematic view)
Nasopharyngeal cooling (Fig. 2) can block the activity of the thermoregulatory center, located in the hypothalamus, which is especially relevant in our febrile septic patients.
Results. Brain and kidney cooling for 24–72 hours contributed to the complete disappearance/prevent symptoms of toxic encephalopathy and renal failure, as well as hyperthermia syndrome and malignant fever. This will reduce the length of stay of patients in ICU and greatly reduce the costs associated with the treatment of septic patients. There was no case of death. All patients fully recovered and returned to normal activities.
Conclusions. Brain and kidney cooling in according to our method allowed to obtain good results in the treatment of patients with toxic encephalopathy, malignant hyperthermia, septic shock.
Конец формы.
1004
BRAIN-0056
Non-Registered Abstracts
Non-Registered Abstracts
GINSENOSIDE-RD IS EFFICACIOUS AGAINST ACUTE ISCHEMIC STROKE BY SUPPRESSING MICROGLIAL PROTEASOME-MEDIATED INFLAMMATION
M. Shi1 and X Liu1
1Department of Neurology, Xijing Hospital The Fourth Military Medical University, Xi'an, China
Abstract
Background and Purpose: A great deal of attention has been paid to neuroprotective therapies for stroke. Our recent TWO clinical trials showed that ginsenoside-Rd (Rd), a monomeric compound from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious in the treatment of ischemic stroke. To better understand the advantage of Rd, here we conducted a pooled analysis of these two trials and further explored possible neuroprotective mechanisms of Rd.
Methods: To increase the statistical power, data from 199 patients with acute ischemic stroke in the first trial and 390 in the second were pooled and reanalyzed to assess the efficacy and safety of Rd. Animal stroke models were used for studying the underlying mechanisms.
Results: The pooled analysis showed that compared with placebo group, Rd was associated with a reduction of patients' disability at day 90 assessed by mRS score and reduced neurologic deficits at day 15 assessed by NIHSS score and at days 15 and 90 by BI score. On animal ischemic stroke models, late administration of Rd (4 h after stroke) was found to inhibit ischemia-induced microglial activation. Rd could decrease the expression levels of various proinflammatory cytokines and suppress IκBα phosphorylation and NF-κB nuclear translocation. An in vitro proteasome activity assay showed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was revealed to have less side effects than glucocorticoid.
Conclusions: Our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation.
1005
BRAIN-0591
Non-Registered Abstracts
Non-Registered Abstracts
MECHANISMS UNDERLYING IMPAIREMENT OF CEREBRAL AUTOREGULATION IN HYPERTENSIVE RATS
S.S. Sindeev1, OA Sindeeva1 and EM Zinchenko1
1Biology, Saratov State University, Saratov, Russia
Abstract
Objectives: Well known, that cerebral blood flow (CBF) is weakly depends on peripherial blood pressure. That fact caused by cerebral autoregulation [1], but it also known that in some pathological states (Alzheimer desease, cerebral hemorrhages, etc.) autoregulation became insufficient [2]. Until now it is undiscovered how peripheral blood pressure affects on CBF in normal and hypertension states [3]. To better understanding relationship between peripheral and cerebral circulation we studied here changes in CBF in acute and chronic hypertensive states.
Methods: To induce acute increase in peripheral mean blood pressure (MAP) we administered phenylephrine (PE) in different doses (0.25 – 0.5 – 1 µg/kg, iv) to normotensive (n = 10) and hypertensive rats (n = 10). To induce two kidney, one clip (2K1C) hypertension rats were clipped at the left renal artery with a silver clip. The rats were instrumented with polyethylene catheters for monitoring MAP using PowerLab system. CBF changes evaluated using laser speckle imaging system. To assessment of expression of structural elements of brain blood barrier we used immunofluorescence and immunoblotting.
Results: PE administration caused the dose-depended increase in MAP in both normotensive and hypertensive rats but the magnitude of pressure response was greater in normotensive rats compared with hypertensive animals. The recovery after phenylephrine-induced increase in MAP was longer in hypertensive rats than in normotensive ones.
CBF remain unchanged in normotensive rats despite significant dose-depended increase in MAP by 15%-27%-52%, respectively. In contrast to normotensive rats, hypertensive rats demonstrated essential CBF response related to MAP changes. So, small dose of PE is accompanied by moderate MAP response (12%, p < 0.05) and, in parallel, increase in CBF by 17% (p < 0.05). The high dose of PE caused significant increase in MAP (32%, p < 0.05) that was associated with increase in CBF (24%, p < 0.05).
We found less expression of structural elements of BBB such as clauding-5, occluding, collagen IV, laminin and increase in permeability of BBB to small (3 kDa) but not large albumins (70 kDa) in hypertensive rats compared with normotensive rats.
Conclusion: Hypertension is accompanied by increase in permeability of BBB with decrease in expression of tight junction’s and basal lamina proteins of BBB. Interruption of BBB in hypertensive rats is associated with impairment of cerebral autoregulation: even moderate peripheral pressure responses cause pronounced increase in CBF. These results allow to conclude that hypertension-induced interruption of BBB can be one of important mechanism underlying impairment of cerebral autoregulation.
Aknowledgements: This work supported by grant of President of Russian Federation, agreement MD-2216.2014.4; RFBR grant 14-02-00526-a.
References
Lassen N A. Cerebral blood flow and oxygen consumption in man. // Physiological Reviews. - 1959, Vol. 39(2). - P. 183–238.Bruder N., Pellessier D., Grillot P. Cerebral Hyperemia During Recoveryfrom General Anesthesia in Neurosurgical Patients // Anesthesia &Analgesia. – 2002. Vol. 94. - no. 3. P. 650–654.Lucas S.J., Tzeng Yu.C., Galvin S.D. et al. Influence of Changes in Blood Pressure on Cerebral Perfusion and Oxygenation // Hypertension. – 2010. - Vol. 55. - P. 698–705.
1006
BRAIN-0192
Non-Registered Abstracts
Non-Registered Abstracts
ROLE OF THE CLINIC SCALE, FOR THE IDENTIFICATION STAGE OF THE COGNITIVE DYSFUNCTION IN PATIENTS WITH POST-TRAUMATIC ENCEPHALOPATHY
N. Sokhibnazarov1 and F Muratov1
1Neurology, Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
Objective: To study the value of various clinical scales to determine the degree of cognitive dysfunction in patients with post-traumatic encephalopathy, during the neuroprotective therapy.
Material methods: The study included 30 patients (21 male and 9 female) who are hospitalized in the neurology department of TMA from the (2013–2014), aged 30 to 55 years (middle age 43,2 ± 7,4 years) suffering with post-traumatic encephalopathy. To assessment neurological status used brief scale to assessment cognitive status (MMSE), the Monreal Assessment Scale (MAS). Patients were divided into 2 groups: the main group consisted of 15 patients with traditional therapy was appointed «Gliatilin» during the 2 weeks. The control group consisted of 15 patients who received only conventional therapy without «Gliatilin».
Results: In the study group patients, who take «Gliatilin» cognitive function are improved (memory, thinking, comprehension) to 38 % than in the control group. It was found that prior to treatment, patients in the study group took 20.8 on the MMSE, and 20.9 point from the MAS. Patients in the control group, respectively, 20.5 and 20.6. After treatment, the patients of the main group on the MMSE score increased to 28.3 points, patients in the control group score been 24.2 points. By «MAS» the study group scored 25.6 points, patients in the control group 22.4 points.
Conclusions:
1. The use of scales to determine the cognitive dysfunctions enables to improved identification degree of cognitive dysfunctions.
2. The use of a neuroprotective drug «Gliatilin» in patients with post-traumatic encephalopathy to improved the condition of patients and reduce the severity of the degree of cognitive impairment, frequent in this pathology.
References
Ibodullaev Z.R. Nervous diseases. Uzbekistan: FAN VA TEXNOLOGIYA UNIT ENTERPRISE, 2014.Majidova Y.N. Samigova D.A. Neurology journal. Treatment for childs with traumatic encephalopathy by perinatal affect of nervous system. Uzbekistan. 2014(1) 4–5 pp.
1007
BRAIN-0091
Non-Registered Abstracts
Non-Registered Abstracts
SALUTARY EFFECT OF PROGESTERONE IN TRAUMATIC BRAIN INJURY
Z. soltani1, B Mofid2, N Shahrokhi1, M Khaksari3, S Karamouzian2, N Nakhaee4 and M Ahmadinejad5
1Neuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences, kerman, Iran
2Dept. of Neurosurgery, Kerman Hospital of Shahid Bahonar, kerman, Iran
3Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences, kerman, Iran
4Dept. of Social Medicine, Medical School of Afzalipour Kerman University of Medical Sciences, kerman, Iran
5Dept. of Intensive Care Unit, Kerman Hospital of Shahid Bahonar, kerman, Iran
Abstract
Objective: The sex hormone progesterone has been shown to improve outcomes in animal models with traumatic brain injury (TBI). The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with diffuse and acute TBI.
Methods: A prospective, randomized, double-blind trial of progesterone was conducted in our teaching hospital. A total of 50 patients with diffuse acute TBI who arrived within 4 hours of injury with a Glasgow Coma Score ≤ 12 were enrolled in the study, when their family consented. In a randomized style 25 received progesterone (1 mg/kg per 12 h for 5 days) and 25 did not. The primary efficacy endpoint was the Glasgow Outcome Scale score 3 months after brain injury. Secondary efficacy endpoint included the mortality.
Results: The demographic characteristics, and the mechanism of injury were similar for the two groups. After 3 months of treatment, the Glasgow Outcome Scale score analysis exhibited more favorable outcome among the patients who were given progesterone compared with the control individuals (P = 0.056). The mortality rate of the control group was 20.8%, whereas any of patients in progesterone group did not die. Instances of complications and adverse events associated with the administration of progesterone were not found in any of patients.
Conclusion: Our data suggest that the administration of progesterone for TBI patients improved neurologic outcome for up to 3 months and reduced mortality. These results indicate that progesterone can considered as a promising neuroprotective drug.
1008
BRAIN-0692
Non-Registered Abstracts
Non-Registered Abstracts
NEUROLOGICAL COMPLICATIONS IN ICU AFTER ON-PUMP CARDIAC SURGERY: A CHINESE STUDY
T. Sosorburam1, L Yao1 and P Xiao2
1Anesthesiology, Tongji Medical College, Wuhan, China
2ICU, Tongji Medical College, Wuhan, China
Abstract
Objectives: Despite having advanced medical care and surgical techniques, neurological complications remain significant causes of postoperative mortality and morbidity in patients underwent cardiac surgery. Whether anesthetic drugs influence the outcome or not is still unclear. Therefore, we conduct the research to determine effects of different anesthetic drugs.
Method: The study was conducted at Union Hospital, China from May 2013 to December 2014. Total 120 patients, who are undergoing on-pump cardiac surgeries without any history of cerebrovascular diseases are recruited. The subjects randomly selected into two most commonly used anesthetic agents groups: volatile anesthetic/VA/ or total intravenous anesthetic/TIVA/ groups. Evaluation of major neurological and physiological dysfunctions were recorded until the patient discharged from the hospital. Comparisons between the groups were analyzed using the t-Student test, and P values of less than 0.05 were considered statistically significant.
Results: There was no significant difference found between the demographics data, intraoperative monitoring and cerebral protective measures between the groups. The incidence of postoperative stroke and postoperative delirium were 2.5% and 5.8% in TIVA group and 3.7% and 6.4% in VA group. Early mortality was higher in VA (4.3% vs 3.5%). Multivariate analysis revealed that postoperative cognitive disorder was associated with longer duration of cardiopulmonary bypass (mean time 132 ± 2.4 min in VA vs 118 ± 4.8 min in TIVA). Another significant difference was transient ischemic attack, which was 7.1% in VA and 6.5% in TIVA. The hospital length of stay and ICU stay were longer in VA group (14.1 and 5.2 days vs 12.3 and 6.2 days).
Conclusion: TIVA associated with lower postoperative mortality and morbidity than VA. The advantage of TIVA over VA is evident regarding interference with neurological and cognitive disorders. However, all the potential neuroprotective effect of TIVA cannot be measured by single anesthetic drug or technique, TIVA appears to be the first choice for on-pump cardiac surgery. We suggest further systemic and multi-centered study should be conducted to implement guidelines regarding the neuroprotective anesthesia.
1009
BRAIN-0918
Non-Registered Abstracts
Non-Registered Abstracts
SNORING AS A RISK FACTOR OF STROKE AMONG FILIPINOS: A CASE CONTROL STUDY
A. Tan1, J Navarro1, A Baroque1 and I David1
1Neurology & Psychiatry, University of Santo Tomas Hospital, Manila, Philippines
Abstract
Objective: The study described the association between stroke and snoring among Filipinos.
Methodology: This case-control study included 109 cases with first-ever stroke and 109 matched control subjects for age, sex and at least two stroke risk factors. A structured interview was done using the validated Berlin Questionnaire in Filipino to identify snoring, daytime sleepiness and stroke risk factors. Univariate odds ratios (OR) for stroke associated with snoring were calculated and significance was assessed.
Results: The case and control groups were matched for age (±2 years), sex and at least two stroke risk factors, which showed no significant difference among groups. There was a significant association between stroke patients who snore compared to controls [OR 31, CI 95% (10.66–90.05)]. The Berlin questionnaire stratified the risk of having sleep apnea among snorers in both groups [OR 3, CI 95% (1.72–5.99].
Conclusion: The study validated that snoring alone is a significant risk factor for stroke.
1010
BRAIN-0099
Non-Registered Abstracts
Non-Registered Abstracts
THERAPEUTIC HYPOTHERMIA IN SEVERE TRAUMATIC BRAIN INJURY
A. Tomar1, C Thomas1, R Talukder1, K Carr1, A Parra1 and A Seifi1
1Neurosurgery, The University of Texas Health Science Center at San Antonio, San Antonio, USA
Abstract
Background: Traumatic brain injury (TBI) is a common and often devastating injury leading to high intracranial pressure (ICP). Therapeutic hypothermia (TH) is one of the few possible therapeutic options in refractory high ICP. We sought to determine the efficacy of TH in controlling high ICP and to find predictors of functional outcome in severe TBI.
Materials and Methods: Retrospective study conducted at University Hospital in San Antonio, TX from 2011–2014. All severe TBI patients were assessed via an imaging TBI score. The primary outcome measure was ICP control and modified Rankin Scale (mRS) at discharge.
Results: During the study period, 77 patients met inclusion criteria, 19 underwent TH and 58 did not. There was no significant difference for age, gender, and ethnicity (P > 0.5). Patients in TH group had significantly higher imaging TBI score, specifically more brain edema (P = 0.001), SDH (P = 0.006) and IVH (P = 0.001), and higher duration of intractable ICP (P = 0.011). There was no significant difference in hospital length of stay (P = 0.541), mRS at discharge (P = 0.082), and mortality (P = 0.139). In multivariate analysis a “TBI scale” using the 24 hr GCS, age > 40, presence of SAH, EDH, and edema on imaging score were the best combination to predict mRS at discharge and ICP control (>80% sensitivity and specificity). Higher “TBI scale” was significantly associated with mRS < 3 at discharge (P = 0.028) and ICP control (P = 0.001). Hypothermia was not significantly associated with mRS < 3 at discharge (P = 0.892), but associated with higher intractable ICP (P = 0.003).
Conclusions: Our study showed that patients with severe TBI who underwent TH usually had higher imaging TBI score. Although TH doesn't show a direct improvement in the outcome of severe TBI, a mixture of parameters including 24 hr GCS, age > 40, EDH, SAH and brain edema can predict severe TBI outcome.
1011
BRAIN-0910
Non-Registered Abstracts
Non-Registered Abstracts
INTRACRANIAL VENOUS HEMODYNAMICS AND RUPTURE OF CEREBRAL ANEURYSM
F. Tsai1, KW Lee2, WL Chen2, CK Liu2, CL Ku2 and S Chen1
1Imaging Research Center, Taipei Medical University, Taipei, Taiwan
2Imaging Research Center, Chang-Hua Christian Hospital, TaipeChang-Hua, Taiwan
Abstract
Objectives: Many uncertainty and inconsistent etiologies of cerebral aneurysmal rupture even wide spectra of factors being reported. Our observation elucidate the potential new factor of cerebral aneurysmal rupture with cerebral venous pressure gradient.
Material and Methods: Retrospectively reviewed 52 were treated with coil embolization with or without cerebral aneurysmal rupture. seventeen male and thirty female were recruited in this study. Color coded quantitative cerebral angiography were performed during coil therapeutic procedure. Cerebral venous circulation were measured with this quantitative cerebral angiography.
Result: Ruptured cases had shorter and symmetrical cerebral venous circulation time (p
Conclusion: Symmetry and shorter cerebral venous circulation in dysplasia venous outlet may play a potential new factor for cerebral aneurysmal rupture.
Right Circulation: CCT Standard deviation Standard error
Symmetry(mm) 18 10.885 2.493 0.487
Asymmetry(mm) 34 12.102 2.452 0.577
Left circulation:
Symmetry(mm) 18 10.680 2.818 0.445
Asymmetry(mm) 34 10.831 2.151 0.507
Diameter of Jugular Vein:
Symmetry(mm) Right 9.13 Left 8.08
Asymmetry(mm) Right 8.81 Left 6.11
CCT: Cerebral Circulation Time
1012
BRAIN-0276
Non-Registered Abstracts
Non-Registered Abstracts
METABOLIC SHIFTS IN NORMAL-APPEARING CHILDREN BRAIN CORTEX IN ACUTE PERIOD OF SEVERE TBI
N.A. Semenova1, MV Ublinskiy1, TA Akhadov1 and IA Melnikov1
1radiology, Children's Clinical and Research Institute Emergency Surgery and Trauma, Moscow, Russia
Abstract
Background: The aim of this study is to reveal and characterize compensatory processes in normal-appearing cortex in acute and subacute period of traumatic brain injury (TBI)
Methods: 34 patients were studied in age from 5 to 16 years (mean age – 12.7 y.). Group of patients consisted of 18 children with severe brain injury (volume of injured tissue was 30–50 ml). 16 age-matched healthy volunteers comprised control group. Phillips Achieva 3.0T scanner was used. MRS-studies were conducted in acute and subacute period of trauma. The area of interest in intact frontal - parietal cortex (volume = 3 cm3) was studied using PRESS (TE = 35 ms, TR = 2000 ms, NSA = 32). The intensities of resonances in each spectrum were normalized to the signal of unsuppressed water. Statistical processing of spectral data was performed using software package Statistica 6.0.
Results: In comparison with control group significant decrease of NAA, increase of Cho, mI and Cr + PCr was found in patients. A direct statistically significant correlation (p < 0,05) between NAA, Cr + PCr and Cho was revealed in both groups: in control group - RNAA-Cr = 0.65, RNAA-Cho = 0.64, RCr-Cho = 0.61; in patients group - RNAA-Cr = 0.82, RNAA-Cho = 0.53, RCr-Cho = 0.66.
Discussion: Increase of Cr + Pcr, Cho signal intensities (in absence of changes in its relaxation characteristics) indicates activation of compensatory processes of choline and creatine synthesis in brain cells. At the same time NAA level is reduced. Existing of NAA-Cr and NAA-Cho correlations and Cr and Cho increase could mean that activation of Cr and Cho synthesis causes the NAA decrease. The scheme of metabolism which is implemented in neurons and explains NAA, Cr, Cho level changes in TBI is proposed. It follows from the scheme that enhancement of compensatory processes activity requires activation of Krebs cycle.
1013
BRAIN-0280
Non-Registered Abstracts
Non-Registered Abstracts
DYNAMICS OF NAA IN MOTOR CORTEX OF NORMAL INDIVIDUALS IN THE PERIOD OF BOLD RESPONSE ON MILISECOND STIMULUS
M. Ublinskiy1, NA Semenova1, IA Melnikov1 and TA Akhadov1
1radiology, Children's Clinical and Research Institute Emergency Surgery and Trauma, Moscow, Russia
Abstract
The aim of this study was the analysis of dynamics of N-acetylaspartate in motor cortex of normal brain after short single stimulus.
Patients and methods. The patients group consisted of 9 healthy mails of 16 – 28 years old in initial stage of schizophrenia and in remission. Phillips Achieva 3.0T scanner was used for the study. Volume of interest in motor cortex was localized on the base of fMRI (EPI BOLD, TR = 3000, TE = 30) as the zone of activation caused by bottom push at the response to single auditory stimuli transmitted with the period of 18 s. The BOLD signal was measured with time resolution of 3 s. 1Н МR spectra were run using synchronization of FID signals acquisition (PRESS, TE = 30 ms TR = 3000 ms) with dynamics of BOLD response after the stimulation at the same paradigm. Auditory stimulus was repeated 98 times and 98 × 7 FID signals were collected. The same method was applied for spectra accumulation in resting state. The signals obtained at time points t = 0, 3, 6, 9, 12, 15, 18 с. after stimulus were summarized. For FID processing homemade program was used. After apodization filtering (LB = 20, GB = −5) FT and manual phase correction amplitudes of resonances were measured. NAA, Cho, Cr signal intensities at the time point t were normalized to the corresponding values at t = 0 and to the volume of activated cells containing in the voxel (measured manually).
Results and conclusions. The BOLD signal demonstrated maximum at the 6th s after target stimulus. The stable values of [NAA], [Cr] and [Cho] were observed in dynamic of resting state. [NAA] significantly decreased at the 12th s after stimulus and returned to initial value at the 15th s. Thus [NAA] minimum delayed relative to maximum of BOLD by 6 s.
Reversible decrease of [NAA] after stimulus presentation might be associated with activation of ASPA reaction. ASPA hydrolyzes NAA into acetate and aspartate. Substantial number of axons express ASPA and AceCS1 (the enzyme catalyzing synthesis of acetyl CoA) [Moffet J. et al. Glia. 2011. 59(10) 1414]. NAA-derived acetate can be converted to acetyl CoA for further metabolism in axons.
Thus the stimulation might lead to NAA hydrolysis to compensate increased metabolic demands.
1014
BRAIN-0621
Non-Registered Abstracts
Non-Registered Abstracts
STRESS-RELATED PATHOLOGICAL CHANGES IN CEREBRAL VENOUS BLOOD FLOW IN NEWBORN RATS ASSESSED BY DOCT
M. Ulanova1, VL.A.D Lichagov2, A Abdurashitov2, M Kassim1, F Ali1 and L Hassani1
1Biology, Saratov State University, Saratov, Russia
2Physics, Saratov State University, Saratov, Russia
Abstract
Objectives: Intracranial hemorrhage (ICH) is a major problem of neonatal intensive care. The incidence of ICH is typically asymptomatic and cannot be effectively detected by standard diagnostic methods. The lack of effective diagnostic technologies for early determination and criteria of ICH risk in newborns explains the high rate of neonatal death and less optimistic neurologic prognosis in infants after ICH. The mechanisms underlying ICH are unknown but there is evidence that stress-related alterations of cerebral venous blood flow (CVBF) may contribute to the pathogenesis of ICH. Therefore, quantitative assessment of CVBF may significantly advance understanding of nature of ICH. The aim of this study was determine the prognostic criteria for pathological changes in pattern of CVBF using Doppler optical coherence tomography (DOCT) in newborn rats with model of stress-induced ICH.
Methods: To induce development of ICH the newborn rats underwent influence of severe sound stress (120 dB, 10 Hz – infrasound, during 2 h). The monitor of CVBF (superior sagittal vein) was performed in anesthetized rats with fixed head using a commercially available Thorlabs swept source optical coherence tomography system OCS1300SS in the masked period of ICH (4 hours after stress) and during ICH (24 hours after stress), the control group included healthy rats.
Results: The results have shown that on latent stage of ICH in stressed rats without ICH the diameter of sagittal vein was in 2.1-fold higher compared with one before stress. The dilation of superior sagittal vein was accompanied by decrease in the speed of blood flow. In rats with ICH these pathological changes in CVBF were greater than in stressed rats on masked period of ICH and especial compared with healthy animals. Adrenaline infusion (10 µg/kg, iv) in healthy rats induced the decrease in diameter of sagittal vein and the increase in speed of blood flow. Note, adrenaline treatment of stressed rats on different stages of ICH was not accompanied by any changes in CVBF.
Conclusion: In summary, in experiments on newborn rats with stress-related ICH using DOCT we have shown that latent stage of ICH (4 h after stress) is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor effect of adrenaline. The incidence of ICH (24 h after stress) was accompanied by progression of early pathological changes in CVBF and development of venous insufficiency. Taking into consideration of this fact, we suggest that the suppression of CVBF related to the severity to the deleterious effect of stress on the brain hemodynamics in newborn rats. These facts allow us to conclude that the venous insufficiency with the loss of vasoconstrictor response to adrenaline is an informative and sensitive component of pattern of CVBF that can be important diagnostic criteria of risk of ICH development in newborns.
A ROLE OF PERFUSION CT IN PATIENTS WITH ACUTE INTERNAL CAROTID ARTERY OCCLUSION FOR EC-IC BYPASS PERFORMANCE
E. Varaksina1, P Chechulov1, V Savello1, I Voznuk1 and A Kostenikov1
1Neurosurgery, Scientific and Research Institute of Emergency Help n.a. I.I. Dzhanelidze, St-Petersburg, Russia
Abstract
Background: Up to date there are no specific data on indications to EC-IC bypass in patients with acute symptomatic internal carotid artery (ICA) occlusion.
Purpose: Studying a role of perfusion CT (PCT) for EC-IC bypass indications definition in patients with acute ICA occlusion.
Materials and methods: EC-IC bypass was performed on 43 patients with acute symptomatic ICA occlusion. Middle age was 57 years (38–71). Average time from hospitalization to surgery – 8,9 days. PCT was performed on 25 patients during 4–6 days from receipt. Control group – 9 patients of comparable age with asymptomatic isolated ICA occlusion.
Results: There were statisticaly significant distinctions in brain perfusion indicators between two groups of investigated. Selection criteria for surgical revascularisation (EC-IC bypass) in patients with acute ICA occlusion were defined: asymmetric increasing of mean transit time (MTT), decreasing of cerebral blood flow (CBF) in combination with relative increase of cerebral blood volume (CBV) on the side of occlusion.
Conclusions: PCT is recommended to be used in selection algorithm for EC-IC bypass in patients with acute symptomatic ICA occlusion. Indicators of brain blood flow velocity decreasing in patients with acute symptomatic ICA occlusion according to PCT data has to be considered as additional criterion of surgical treatment.
1016
BRAIN-0140
Non-Registered Abstracts
Non-Registered Abstracts
A NOVAL NEUROPROTECTIVE AGENT AND ENHANCES COGNITION TREATMENT WITH MANASAMITRA VATAKAM(MMV) DIAGNOSED BY PETCT
V Thirunavukkarasu1 and S. Venkataraman1
1Dept. of Medical Cyclotron, HCG Enterprise LTD, Chennai, India
Abstract
Abstract
Background:Manasamitra vatakam (MMV) as pivotal role against Aluminium induced neuronal apoptosis. Herbo-mineral formulation of MMV prepared by Indian system of Ayurvedic medicine and used to improve cognitive functions against Aluminium induced dysfunction of rats.
Objectives: The study focused MMV as an alternative Ayurvedic medicine against neuronal cell death caused cognitive dysfunction induced by Aluminium treated rats.
Materials and Methods: The study consists of five groups, six animals in each. Male healthy Swiss albino rats (200–220 gm) were used and housed in clean polypropylene cages and maintained the room temperature 23℃ - 25℃ with alternating 12 h light and dark cycles. The animals were treated Aluminium orally and fed with standard pellet diet and clean drinking water. The study was assessed cognitive functions of behavioral parameters like active avoidance and radial arm maze. The whole experimental studies were conducted for 90 days. The biochemical and molecular studies (Western blot, RT-PCR and Immunohistology) were carried out by standard methods.
Results: The results shown that MMV treated animals significantly improved neurotransmitters such as 5-HT and Acetyl Choline as well as cognitive functions of rats and restrain expression of oxidative stress (HSP70) & pro-apoptotic genes like Bcl-2, Bcl-xL and Caspas-3 against Aluminium induced hippocampus region of rat’s brain. In aluminium induced animals were observed pro-apoptosis genes like Bcl-2, Bcl-xL and caspas-3 were significantly expressed high in hippocampus and cerebral cortex of brain regions. Whereas MMV treated animals were observed normal brain with the help of PETCT scan and behavioral activities as on control.
Conclusion: The present study reveals that Herbo-mineral formulation of Manasamitra vatakam (MMV) potentially improved memory function and inhibited oxidative stress, neuronal apoptosis against Aluminium induced neurodegenerative disorder rats.
1017
BRAIN-0715
Non-Registered Abstracts
Non-Registered Abstracts
REGIONAL CORRELATION BETWEEN PCASL PERFUSION AND PIB-PET IN FAMILIAL ALZHEIMER'S DISEASE
D.J.J. Wang1, L Yan1, C Liu2, KP Wong1, SC Huang1, D Wharton1 and J Ringman1
1Neurology, UCLA School of Medicine, Los Angeles, USA
2Neurology, University of Southern California, Los Angeles, USA
Abstract
Objective: [11C]Pittsburgh compound B ([11C]PiB) PET amyloid imaging has been widely used for monitoring amyloid-β deposition, and for evaluating anti-amyloid therapies of Alzheimer’s disease (AD). Tracer kinetic modeling of PiB-PET can yield multiple parameters including R1 (related to tracer delivery or relative perfusion), binding potential (BP) and distribution volume ratio (DVR = BP + 1) of PiB1. Arterial spin labeling (ASL) is a noninvasive MRI technique to measure cerebral blood flow (CBF), and has shown promises as an imaging marker of AD2. The purpose of the present study was to systematically compare ASL perfusion MRI with PiB PET in a cohort of familial AD (fAD) related subjects who are either carriers of PSEN1, PSEN2, or APP mutations or their non-mutation carrying family members.
Methods: Twenty-five fAD related subjects (age 38 ± 12 years, 15F) underwent dynamic 11C-PIB PET/CT scans in list-mode for 70 mins. Raw PET data were reconstructed using ordered subset expectation maximization algorithm. A retrospective image-based movement correction procedure was applied to correct for possible misalignment between CT and PET scans and between PET image frames. All subjects also underwent MRI scans on a Siemens Tim Trio 3T scanner. Pseudo-continuous ASL (pCASL) with 3D background suppressed GRASE sequence was applied for perfusion measurement. Both ASL and PET images were coregistered to the subject’s structural MRI, which were warped to MNI brain template. Tissue time-activity curve was generated for cerebellar gray matter (reference region) and parametric images of relative perfusion (R1) and distribution volume ratio (DVR) were constructed by simplified reference tissue model (SRTM) and Logan graphical method, respectively.
Results: Figure 1 shows the mean rCBF, R1 and DVR images averaged across 25 subjects. R1 and rCBF images show high consistency with each other with high contrast between gray and white matter. DVR images show more uniform spatial distribution between gray and white matter. Voxel-by-voxel correlations between the mean rCBF and mean R1 maps of 25 subjects were calculated for 9 ROIs. Significant correlations between rCBF and R1 were observed in each ROI with an overall mean correlation coefficient of r = 0.65. A reduced correlation with the mean correlation coefficient of 0.4 was acquired between rCBF and DVR. The correlation between the mean rCBF and R1 values across 25 subjects in the 9 ROIs was also calculated. The overall correlation was intermediate (mean r = 0.19). The cross-subject correlation between the mean rCBF and DVR values showed negative correlations with the mean correlation coefficient of r = −0.18.
Discussion: To the best our knowledge, this is the first study to systematically compare ASL perfusion with PiB PET. The similar spatial pattern and significant voxel-wise correlations between rCBF and R1 are expected since both parameters estimate brain perfusion. The negative cross-subject correlation between rCBF and DVR suggest that brain regions with high DVR values may be associated with hypoperfusion. Our data suggest that both ASL and PiB PET can provide valuable imaging markers for AD.
References
Zhou et al Neuroimage. 2007; 36(2):298–312.Alsop et al J Alzheimers Dis. 2010;20(3):871–80.
1018
BRAIN-0784
Non-Registered Abstracts
Non-Registered Abstracts
NEUROPROTECTIVE EFFECTS AND MECHANISM OF POMALIDOMIDE AGAINST TRAUMATIC BRAIN INJURY
J. WANG1, J Wang1, L Yang1 and N Greig2
1Graduate Institute of Med Sci, Taipei Medical University, Taipei city, Taiwan
2Drug Design & Development Section, National Institute on Aging, Baltimore, USA
Abstract
Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease and death worldwide. In response to acute brain trauma, glial cells become activated and secrete pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β). This neuroinflammation plays a crucial role in the secondary tissue damage. Thalidomide has anti-inflammatory property. Its analog Pomalidomide (Pom) has been shown more potent as a TNF-α inhibitor than Thalidomide. The aim of our study is to investigate the effect and window of Pomalidomide (Pom) and 3,6’-dithiothalidomide (3,6’-DT) on functional and histological outcomes and inflammatory cytokine expression after TBI.
We have previously established the rat model of TBI using adult Sprague-Dawley rats subjected to controlled cortical impact (CCI). Five hours or seven hours after TBI, Pom (0.5 mg/kg, i.v.), 3,6’-DT (28 mg/kg, i.p.) or vehicle was administered. Neurological functions were evaluated using swing test, adhesive removal, modified neurological severity scores and beam walking. Contusion volume and neuronal degeneration were measured using cresyl violet and FluoroJade C staining. Levels of TNF-α, IL-1β and IL-6 mRNA were measured by real-time quantitative reverse transcriptase-PCR, protein were estimated by enzyme-linked immunosorbent assay and immunohistochemistry from TBI with or without drug treatment. In vitro, primary rat cortical cultures were treated with H2O2 (300μM) in the presence or absence of various concentration of Pom to investigate whether the drug protects cells from oxidative stress. Cell death was estimated by LDH assays. Neurons, microglia and astrocytes were identified by ICC with specific markers.
Post-injury treatment with Pom significantly improved functional recovery and decreased contusion volume at 24 hours post-injury. The time window is between 5 and 7 hours, and the dose window is between 0.1 and 0.5 mg/kg (i.v.). Pom treatment also reduced the number of degenerating neurons at the contusion site. Pom (50μM) enhanced cell viability against H2O2-induced oxidative stress and reduced microglia activation.
Our data suggest that post-treatment of Pom improves histological and functional outcomes after experimental TBI and reduces inflammatory responses. The pre-clinical results with Pom has a potential for further clinical trial.
1019
BRAIN-0855
Non-Registered Abstracts
Non-Registered Abstracts
MODERATE AND SEVERE HYPOGLYCAEMIA ASSOCIATED METABOLIC CHANGES IN CORTEX AND HIPPOCAMPUS OF MICE
V Pitchaimani1, S Arumugam1, V Karuppagounder1, R Sreedhar1, R Afrin1, M Harima1, H Suzuki1, M Nomoto1, S Miyashita1, T Nakamura1, K Suzuki2 and M Nakamura3, K. Watanabe1
1Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan
2Gastroenterology, Niigata University of Graduate School of Medicine and Dental Sciences, Niigata, Japan
3Cardiology, Yamanashi Prefectural Central Hospital Kofu, Yamanashi, Japan
Abstract
Fasting or starvation (moderate hypoglycaemia) decrease glucose utilization and metabolism in brain. During severe hypoglycemic emergency, the dextrose administration is the first choice and it preserve neuronal metabolism associated with NADPH dependent oxidative stress.
This raises two questions. 1) How the brain decreases glucose metabolism and uptake in moderate hypoglycemia and how it regain glucose metabolism in severe hypoglycemia 2) what mechanism could contribute to oxidative stress.
In this study we investigated the insulin signalling kinases (AKT, Ps6K, and ERK),glycolytic markers (PFK1 and BADser155), glucose transporters (GLUT1and GLUT3) and glutamate reuptake markers (Excitatory amino acid transporter (EAAT2) and Na + K + ATPase) by western blot analysis in moderate hypoglycemic (24 hr. fasting and 2 IU insulin induced hypoglycemia (IIH) at 10 and 30 min) and severe hypoglycemia (IIH at 90 min after experienced seizure like behaviour).
Fasting hypoglycemia (BGL 58.2 mg/dl) decrease insulin signalling kinases and glycolysis and may shifts to HMP shunt to synthesize antioxidant glutathione(GSH). The glucose uptake in neurons may get slightly decreased by GLUT3 and nochange was observed in astrocytic GLUT1.
IIH after 10 min (BGL 67.8 mg/dl) decrease AKT expression and glycolysis and nochange was observed in glucose transporter expression. This raises a question that how the AKT decreases at 10 min. Other reports suggesting that insulin phosphorylate AKT first and then Ps6K in a time dependant manner. We observed a significant increase in Ps6k in hippocampus but not in cortex suggesting that insulin crosses the blood brain barrier first in cortex and phosphorylate AKT and then hippocampus nearly 5 min. Due to the hypoglycemia mediated effect, AKT andglycolysis decrease at 10 min.
IIH after 30 min (BGL 54.80 mg/dl) regained AKT expression and glycolysis and therewas more decrease in GLUT 3 but not significant and no change was observed inGLUT1. Previous reports suggesting that IIH decrease glutamate and restored with other fuels like lactate. NMDA receptor activation increase GLUT3 expression. This indirectly suggesting that IIH at 30 min after decrease GLUT3 expression in neuron by possibly decreasing glutamate.
IIH after 90 min (BGL below 20 mg/dl) has increased insulin signalling but decreased glycolysis and may shifts to HMP shunt but unable to synthesizeglutathione and it restored GLUT 3. The glutathione synthesis require cysteinefrom astrocytes by an ATP dependent mechanism. Other reports suggesting that severe hypoglycemia decreases ATP and thismay increase NADPH dependent oxidative stress during glucose reperfusion. Numerousreports suggesting that severe hypoglycemia increase glutamate. The restored GLUT 3 possibly associated with the increased glutamate mediated NMDA receptoractivation.
This raises another question how the decreased glutamate in 30 min after INS increasedat 90 min after INS. The extracellular glutamate is mainly removed by EAAT2 which functionally associated Na + K + ATPase. We checked the EAAT2 and Na + K + ATPase Ty10and no change was observed. This suggesting that Na + K + ATPase may get phosphorylated at other residue or excess glutamate accumulated by reversed glutamate transport.
1020
BRAIN-0447
Non-Registered Abstracts
Non-Registered Abstracts
DISRUPTED WHITE MATTER INTEGRITY IN PARKINSON'S DISEASE WITH DEPRESSION
J.Y. Wu1, Y Zhang1, WB Wu1 and Y Xu1
1Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Abstract
Depression is one ofthe most commonnon-motor symptoms in Parkinson's disease (PD) which can causefunctional impairment and further reduce the quality of life. But thepathophysiological relationship between PD and depression is still remainsunclear. Increasing evidence suggest that depression in PD is closely relatedto the white matter abnormalities. In this study we investigated whole brainwhite matter integrity in 24 depressed PD patients and 32 non-depressed PDpatients. There was no difference in age, gender, education, disease duration, Hoehn–Yahr stages, Unified Parkinson's Disease Rating Scale scores and Mini-MentalState Examination scores between the two groups. The only difference was the HamiltonRating Scale for Depression score (HDRS). The depressed PD patients groupshowed reduced fractional anisotropy (FA) value in the left superiorlongitudinal fasciculus, inferior longitudinal fasciculus, superior andposteriorof corona radiate, posterior thalamic radiation, sagittal stratum(include inferiorlongitudinal fasciculus and inferior fronto-occipitalfasciculus), stria terminalis, and superior fronto-occipital fasciculus. Inpatients with PD, the HDRS was negativelycorrelated with the FA value in theleft superior fronto-occipital fasciculus (r = −0.691, p = 0.028). This studysuggested that PD patients with depression arecharacterised by decreasedfunctional integration in the left hemisphere. Thesefindings may be helpful forfurther understanding the potential mechanisms underlying depression in PD.
Y. Xie1, A Chan1, A McGirr1, S Xue1, D Xiao1 and T Murphy1
1Psychiatry, University of British Columbia, Vancouver, Canada
Abstract
Wide field of view mesoscopic cortical imaging with genetic encoded sensors enables decoding regional activity and connectivity in anesthetized and behaving mice. However, the temporal kinetics of most genetically-encoded sensors can be suboptimal for in vivo characterization of frequency bands higher than 1 Hz. Furthermore, existing sensors in particular those which measure calcium (genetically encoded calcium indicators; GECIs), can be affected by non-linearities associated with spiking or calcium binding. Here, we demonstrate using in vivo mesoscopic imaging the rapid and robust kinetics of virally transduced (AAV1-synapsin-iGluSnFR) and transgenically expressed glutamate-sensing fluorescent reporter (EMX1:tTA-CamkII: iGluSnFR). In both awake and anesthetized mice we imaged a 8 × 8 mm field of view through an intact transparent skull preparation. iGluSnFR demonstrates rapid and robust kinetics during cortical representation of sensory stimulation, that is then paralleled in spontaneous cortical activity with maps recovered up to alpha frequencies (8–12 Hz). iGluSnFR also resolved other features of sensory processing such as an intracortical re-bound during the processing visual stimuli that was not seen with other GECIs. The regional cortical kinetics of iGluSnFR were more rapid than EMX-GCaMP3, and comparable to the temporal responses seen with RH1692 voltage sensitive dye (VSD), with similar signal amplitude. Regional cortical connectivity detected by iGluSnFR in spontaneous brain activity identified functional circuits consistent with maps generated from EMX-GCaMP3 mice and VSD sensors. The iGluSnFR sensor is a fast genetic-encoded sensor of extracellular glutamate, with potential utility in normal physiology, as well as neurologic and psychiatric pathologies in which glutamatergic abnormalities are recognized.
1022
BRAIN-0047
Non-Registered Abstracts
Non-Registered Abstracts
CONTRIBUTION OF PREOPTIC AREA THERMO TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE IV (TRPV4) CHANNEL IN THERMOREGULATION IN RATS
R. Yadav1, H Mallick1, A Jaryal1 and K Kumari1
1Physiology, All India Institute of Medical Science, Delhi, India
Abstract
Method: The study was conducted in six male Wistar rats. Under thiopentone sodium anesthesia (fourty miligramg/kilogram BodyWeight) a bilateral guide cannula with indwelling styli was implanted with their tips aimed at two mm above the preoptic area as per De Groot’s atlas. A radio transmitter (Data Science International, USA) for the telemetric recording of body temperature was implanted in the abdomen. A K- type thermocouple wire was inserted near the hypothalamus to measure the brain temperature. Brain temperature was recorded at fifteen second interval through a fluke digital thermometer. Tb was recorded telemetrically at fifteen second interval. The temperature was measured from 10.00 to 16.00 h and injection was given at 12.00 h. Temperature data was averaged at fifteen minute epochs. TRPV4 agonist,(GSK1016790A),injection was given bilaterally at the Preoptic area at a rate of 0.1 micro liter /minute using an injector cannula. The site of injection was confirmed histologically. The statistical comparison was made between pre and post injection record at every fifteen minutes using paired t-test.
Result: TRPV4 agonist cause hypothermia in rats
Conclusion: The TRPV4 channel agonist injection in the preoptic area brings about fall in body and brain temperature by stimulating warm sensitive neurons.
1023
BRAIN-0473
Non-Registered Abstracts
Non-Registered Abstracts
EFFECTS OF ALOGLIPTIN ON THE METABOLISM OF NITRIC OXIDE (NO) AND HYDROXY RADICALS IN BRAIN DURING BRAIN ISCHEMIA-REPERFUSION
M. yamazato1, M yamazato2, M Hirayama3, Y Ito3, R Nishioka3, R Nishioka3 and N Araki3
1neurology, Saitama Medical Center, Saitama, Japan
2neurology, Higashimatsuyama Medical Association Hospital, Saitama, Japan
3neurology, Saitama Medical University, Saitama, Japan
Abstract
Purpose: The metabolism of nitric oxide (NO) and hydroxy radicals in the brain of C57BL during brain ischemia-reperfusion is investigated under treatment with alogliptin, an innovative drug and one of the DPP4 inhibitors for controlling incretin levels in blood glucose metabolism.
Methods: (1) C57BL treated with alogliptin 45 mg/kg/day (n = 5) for 4 weeks and and the control group (n = 8) were used. Both NO production and hydroxyl radical metabolism were continuously monitored by in vivo microdialysis. Microdialysis probes were inserted into the bilateral striatum. A Laser Doppler probe was placed on the skull surface. Blood pressure, blood gases and temperature were monitored and maintained within normal ranges throughout the procedure. Forebrain cerebral ischemia was produced by occlusion of both common carotid arteries for 10 minutes. Levels of nitric oxide metabolites, nitrite () and nitrate (), in the dialysate were determined using the Griess reaction. Right side is for 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA). Samples were measured by the salicylic rate trapping method. Three days thereafter, we removed the brain and made the slide, and divided the extent of ischemia injury into three “stages” (“severe ischemia group”, “moderate ischemia group” and ‘survive group”), according to the nucleus' degree of transformation and degree of staining. Considering as the survival rate the rate of the “survive group” that represents the percentage of the sum, we carried out a comparative examination among the three groups.
Results:
(1) BloodPressure:Alogliptin group (73.2 ± 10.6 mmHg; mean ± SD) showed significantly lower than those of the control group (88.3 ± 7.35).20 minutes after the start of reperfusion (p < 0.05).
(2) Cerebral Blood Flow (CBF): There were no significant differences between the groups.
(3) Nitric oxide metabolites: 1) ; Alogliptin group (0.86 ± 0.2, 0.73 ± 0.2, 0.7 ± 0.2 mol/L) showed significantly lower level than those of the control group(1.17 ± 0.1, 0.99 ± 0.2, 1.1 ± 0.2) pre-ischemia, ischemia and 50 minutes after the start of reperfusion (p < 0.05) (Figure 1).
2) ; There were no significant differences between the groups.
(4) Hydroxyl radical; Alogliptin group (96.3 ± 3.3, 87.6 ± 9.0, 84.8 ± 7.2, 84.3 ± 7.2 %) showed significantly lower level than those of the control group (100 ± 1.1, 98.7 ± 2.6, 98.8 ± 3.4, 98.2 ± 4.6) ischemia and 80–120 minutes after the start of reperfusion (p < 0.05) (Figure 2).
(5) Pathology; There were almost significant differences between the groups (P = 0.051).
Conclusion: It has been suggested that Alogliptin can affect the nitric oxide metabolism in the brain after cerebral ischemia-reperfusion in the C57BL mice.
1024
BRAIN-0050
Non-Registered Abstracts
Non-Registered Abstracts
CT PERFUSION IMAGING IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACKS: A PROSPECTIVE CLINICAL STUDY
L. Yuxia1, YQ Li2 and Y Han3
1Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China
2Department of Neurology, Tangshan Worker’s Hospital Clinical Medical College of Hebei Medical University, Tangshan, China
3Department of Neurology, Xuan Wu Hospital Capital Medical University, Beijing, China
Abstract
Objective: Transient ischemic attacks (TIA) are an emergency in neurology, and it can be progressed to ischemic stroke promptly if not timely diagnosis and treatment. There are no positive findings in routine computerized tomography (CT)/magnetic resonance imaging, and is there really any abnormality at the TIA interphase in radiologic imaging? A prospective clinical study was performed to evaluate the cerebral blood flow in patients with TIA using cerebral CT perfusion imagine (CTP), and investigating the risk factor of CTP abnormality.
Methods: CTP and CT angiography (CTA) were performed on all 69 cases of TIA patients, and got parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and the cerebral artery stenosis. Compared the affected lateral with the contra lateral to get information of cerebral ischemia, and analysis of the relationship between parameters of CTP and the clinical symptoms, investigate the risk factor of CTP abnormality.
Results: Persisting abnormal perfusion changes corresponding to clinical symptoms were found in 52 cases with prolonged TTP and MTT, CBF and CBV drop was not statistically significant between both groups. Cerebral hypoperfusion correlated with increased NIHSS score of TIA onset, the duration of TIA onset, and the cerebral artery stenosis in TIA patients.
Conclusion: TTP, MTT maps in CTP had a high sensitivity on showing cerebral perfusion abnormalities. The more serious of TIA onsets in clinical, the higher ratio of CT perfusion abnormality.
References
EliasziwMKennedyJHillMD. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease [J]. CMAJ2004; 170: 1105–1109.中华神经科学会.各类脑血管疾病诊断要点.中华神经科杂志 [J], 1996,29(6):379–380.LevMHRomeroJMGoodmanDN. Total occlusion versus hairline residual lumen of the internal carotid arteries: accuracy of single section helical CT angiography [J]. AJNR Am J Neuroradio2003; 24: 1123–1129.SparaciaGLaiaAAssadiB. Perfusion CT acute stroke: predictive value of perfusion parameters in assessing tissue viability versus infarction[J]. Radiol Med2007; 112(1): 113–122.[M].第5版.北京:人民卫生出版社,2004,7:131–141.MilesKA. Measurement of tissue perfusion by dynamic computed tomography[J]. B r J Radiol1991; 64(5): 409–412.FlohrTGSchallerSStierstorferK. Multi-detector row CT systems and imaging-reconstruction techniques[J]. Radiology2005; 235(3): 756–773.LeeTYBeleskyVKalaposP. CT perfusion imaging in cerebral ischemia[J]. Stroke2005; 36(1): 1–3.
1025
BRAIN-0917
Non-Registered Abstracts
Non-Registered Abstracts
BRAIN MAPPING OF THE METABOLISM CHANGES: A PET/CT STUDY IN THE PATIENTS WITH NON-SMALL CELL LUNG CANCER BEFORE TREATMENT
W. Zhang1, N Ning2, X Li3, J Ma1, Y Guo1 and J Yang1
1Radiology Department, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
2Nuclear Medicine Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
3Department of Biomedical Engineering, The Key Laboratory of Biomedical Information Engineering of the Ministry of EducationThe School of Life Science and Technology of Xi’an Jiaotong University, Xi'an, China
Abstract
Objective: Cancer research has largely focused on neurobiology [1]. The neurobiological view of cancer aetiopathogenesis suggests that cancer information is conveyed by neural and humoral pathways to the special brain structures, and that brain might consequently modulate the neuroendocrine-immune system to regulate tumor growth [1–5]. The present study aimed to observe brain glucose metabolism pattern in non-small cell lung cancer (NSCLC) patients and to explore the changes of the brain metabolism caused by the lung cancer.
Methods:18F-FDG PET/CT of 83 NSCLC patients (35 to 69 years, mean = 53.65 ± 7.81 years old, male/female = 58/25) and 76 healthy controls (age from 33 to 67 years, mean = 51.83 ± 8.01 years old, male/female = 51/25) were performed in a resting state. The malignant group consisted of histopathologically proven cases with NSCLC by pneumocentesis, surgery or thoracoscope (clinical stage 1 [n = 16], 2 [n = 15], 3 [n = 28], or 4 [n = 24]). The pathological types were 51 adenocarcinoma, 27 squamous carcinoma and 5 bronchioloalveolar carcinoma. Images were registered to the atlas by using the statistical parametric mapping (SPM) software. The brain normalized metabolic differences between groups (patients versus controls, clinical stages, adenocarcinoma group versus squamous carcinoma group) were analyzed by two samples t-test and multivariate-test with SPSS 13.0 software.
Results: Significant differences were found in brain glucose metabolisms between patients and controls (p < 0.01). The hypermetabolism regions included the orbital part of right inferior frontal gyrus, insular, basal ganglia, thalamus, hippocampus, amygdala and cerebellum, while the hypometabolism regions included left superior parietal lobule, bilateral inferior parietal lobule, and left fusiform gyrus (figure 1). The multivariate-test showed no significant differences among clinical stages or between adenocarcinoma and squamous carcinoma groups.
Conclusions: There were abnormal glucose uptakes in brain regions in NSCLC patients, and different clinical stages and pathological types (just for adenocarcinoma and squamous carcinoma) were not considerable factors affecting on the brain FDG uptake. The hypermetabolisms in the brain interpret a tumor-to-brain pathway on central neuromodulation of lung malignancy. The brain hypometabolisms associated with visual and spatial orientation functions may be caused by cancer related inflammation.
Figure 1. Abnormal glucose metabolisms in the non-small cell lung cancer patients. Both decreased and increased brain glucose uptake are observed (p<0.01). Color bar indicates t-values; L: left; R: right.
References
MravecBGidronYHulinI. Neurobiology of cancer: Interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain. Semin Cancer Biol2008; 18(3): 150–63.BenvenisteH. Brain metabolomic profiles of lung cancer patients prior to treatment characterized by proton magnetic resonance spectroscopy. Int J Clin Exp Med2012; 5(2): 154–64.OndicovaKMravecB. Role of nervous system in cancer aetiopathogenesis. Lancet Oncol2010; 11(6): 596–601.Armaiz-PenaGN. Neuroendocrine modulation of cancer progression. Brain Behav Immun2009; 23(1): 10–5.GolanH. Brain mapping of patients with lung cancer and controls: inquiry into tumor-to-brain communication. J Nucl Med2009; 50(7): 1072–5.
1026
BRAIN-0432
Non-Registered Abstracts
Non-Registered Abstracts
CORRELATIONS OF DEPRESSION WITH OTHER NON-MOTOR SYMPTOMS IN PD
Y. zhang1, J wu1 and YU.N xu1
1Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Abstract
Depression is a frequent behavioral disorder in patients with Parkinson’s disease(PD). Many research of depression has been investigated in PD. Nevertheless, whether depression is related to other non-motor symptoms in PD is unknown. Our objective was to determine the prevalence and features of depression and associated factors in a group of PD patients. Eighty five PD patients participated in the study. Depression, motor symptoms, and other non-motor symptoms were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with depression. Thirty seven patients (43.5%) were diagnosed as depression. Depressive patients had significantly more lower cognitive status than non-depressive patients. When considering non-motor symptoms, depression was significantly associated with fatigue and anxiety, both of which were more prevalent in depressive patients than in non-depressive patients. Depression was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, depression appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anxiety.
1027
BRAIN-0049
Non-Registered Abstracts
Non-Registered Abstracts
FORCED LIMB-USE ENHANCED NEUROGENESIS AND BEHAVIORAL RECOVERY AFTER STROKE IN THE AGED RATS
C. Zhao1 and H Qu1
1Neurology, The first hospital of China Medical University, Shenyang, China
Abstract
Constraint-induced movement therapy (CIMT) after stroke enhances not only functional reorganization but also structural plasticity of the brain in the adult rats. We examined whether forced limb-use which mimicked CIMT could influence ischemia-induced neurogenesis, apoptosis and behavioral recovery in the aged rats. Aged rats were divided into a sham group, an ischemia group, and an ischemia group with forced limb-use. Focal cerebral ischemia was induced by injection of endothelin-1. Forced limb-use began on post-stroke day 7 by fitting a plaster cast around the unimpaired upper limbs of rats for 3 weeks. Behavioral recovery was evaluated by tapered/ledged beam-walking test on postoperative day 32. The expression of doublecortin (DCX), neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP) and Iba-1 were measured by single or double immunohistochemistry, and apoptosis was measured by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The production of neuroblasts in the subventricular zone (SVZ) was significantly increased after stroke. Forced limb-use enhanced the proliferation of newborn neurons in the SVZ, as well as increased the long-term survival of newborn neurons. Furthermore, forced limb-use suppressed apoptosis and improved the motor functions after stroke in the aged rats. Forced limb-use exerted few effects on inflammation. Neither the number nor dendritic complexity of newborn granule cells in the hippocampus was affected by forced limb-use. Forced limb-use is effective in enhancing neurogenesis and behavioral recovery after stroke even in the aged rats.
