Systemic Kainic Acid (KA) administration has been used to induce experimental temporal lobe epilepsy in rats. The aim of this study was to evaluate the neuroprotective effect of rosemary extract (RE, 40% Carnosic acid) against KA-induced neurotoxicity in hippocampus and impaired learning and memory. Animals received a single dose of KA (9.5 mg/kg) intraperitoneally (i.p.) (KA group) and were observed for 2 h and were scored from 0 (for normal, no convulsion) to 5 (for continuous generalized limbic seizures). RE (100 mg/kg, orally) was administered daily for 23 days, starting a week before KA injection (KA+RE group). Neuronal degeneration in hippocampus was demonstrated by using Fluoro-Jade B immunofluorescence. The number of pyramidal cells in hippocampus was evaluated by Nissl staining. Also, the Morris Water Maze and Shuttle box have been used to assess spatial memory and passive avoidance learning, respectively. Our results revealed that, after treatment with RE, neuronal loss in CA1 decreased significantly in the animals in KA+RE group. The Morris water navigation task results revealed that spatial memory impairment decreased in the animals in KA+RE group. Furthermore, results in Shuttle box test showed that passive avoidance learning impairment significantly, upgraded in the animals in KA+RE group. These results suggest that RE may improve the spatial and working memory deficits and also neuronal degeneration induced by toxicity of KA in the rat hippocampus, due to its antioxidant activities.
AltinierG., SosaS., AquinoR.P., MencheriniT., Della LoggiaR. and TubaroA., Characterization of topical antiinflammatory compounds in Rosmarinus officinalis L., J Agric Food Chem.55(5) (2007), 1718–1723. doi:10.1021/jf062610+.
2.
AmaralG.P., de CarvalhoN.R., BarcelosR.P., DobrachinskiF., Portella RdeL., da SilvaM.H., LugokenskiT.H., DiasG.R., da LuzS.C., BoligonA.A., AthaydeM.L., VillettiM.A., Antunes SoaresF.A. and FachinettoR., Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats, Food Chem Toxicol.55 (2013), 48–55. doi:10.1016/j.fct.2012.12.038.
3.
AzadN., RasoolijaziH., JoghataieM.T. and SoleimaniS., Neuroprotective effects of carnosic acid in an experimental model of Alzheimer's disease in rats, Cell J.13 (2011), 39–44.
4.
BabaS., OngaK., KakizawaS., OhyamaK., YasudaK., OtsuboH., ScottB.W., BurnhamW.M., MatsuoT., NagataI. and MoriN., Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity, Sci Rep.6 (2016), 27511. doi:10.1038/srep27511.
5.
BozziY., ValloneD. and BorrelliE., Neuroprotective role of dopamine against hippocampal cell death, Journal Neurosci.20(22) (2000), 8643–8649.
6.
CasselA., MorrisR., KoutroumanidisM. and KopelmanM., Forgetting in temporal lobe epilepsy: When does it become accelerated?, Cortex.78 (2016), 70–84. doi:10.1016/j.cortex.2016.02.005.
7.
ChanS.L., LiuD., KyriazisG.A., BagsiyaoP., OuyangX. and MattsonM.P., Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells, J Biol Chem.281(49) (2006), 37391–37403. doi:10.1074/jbc.M605552200.
8.
Del CampoJ., AmiotM.J. and Nguyen-TheC., Antimicrobial effect of rosemary extracts, J Food Prot.63(10) (2000), 1359–1368. doi:10.4315/0362-028X-63.10.1359.
9.
DoolaegeE.H., VossenE., RaesK., De MeulenaerB., VerhéR., PaelinckH. and De SmetS., Effect of rosemary extract dose on lipid oxidation, colour stability and antioxidant concentrations, in reduced nitrite liver pâtés, Meat Sci.90(4) (2012), 925–931. doi:10.1016/j.meatsci.2011.11.034.
10.
ErmakG. and DaviesK.J., Calcium and oxidative stress: From cell signaling to cell death, Mol Immunol.38(10) (2002), 713–721. doi:10.1016/S0161-5890(01)00108-0.
11.
Estrada SánchezA.M., Mejía-ToiberJ. and MassieuL., Excitotoxic neuronal death and the pathogenesis of Huntington's disease, Arch Med Res.39(3) (2008), 265–276. doi:10.1016/j.arcmed.2007.11.011.
12.
FerkanyJ.W., ZaczekR. and CoyleJ.T., Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors, Nature.298(5876) (1982), 757–759. doi:10.1038/298757a0.
13.
GascoigneM.B., SmithM.L., BartonB., WebsterR., GillD. and LahS., Accelerated long-term forgetting in children with temporal lobe epilepsy, Neuropsychologia.59 (2014), 93–102. doi:10.1016/j.neuropsychologia.2014.04.012.
14.
GeorgeS. and ChaturvediP., Protective role of Ocimum canum plant extract in alcohol-induced oxidative stress in albino rats, Br J Biomed Sci.65(2) (2008), 80–85. doi:10.1080/09674845.2008.11732802.
15.
GinsbergM.D., Neuroprotection for ischemic stroke: Past, present and future, Neuropharmacology.55(3) (2008), 363–389. doi:10.1016/j.neuropharm.2007.12.007.
16.
GurbanovaA.A., AkerR.G., SirvanciS., DemiralpT. and OnatF.Y., Intra-amygdaloid injection of kainic acid in rats with genetic absence epilepsy: The relationship of typical absence epilepsy and temporal lobe epilepsy, J Neurosci.28(31) (2008), 7828–7836. doi:10.1523/JNEUROSCI.1097-08.2008.
17.
HalliwellB., Oxidative stress and neurodegeneration: Where are we now?, J Neurochem.97(6) (2006), 1634–1658. doi:10.1111/j.1471-4159.2006.03907.x.
18.
HeathP.R., TomkinsJ., InceP.G. and ShawP.J., Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection, Neuroreport.13(14) (2002), 1753–1757. doi:10.1097/00001756-200210070-00012.
19.
HritcuL., NoumedemJ.A., CioancaO., HancianuM., KueteV. and MihasanM., Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta (1–42) rat model of Alzheimer's disease, Cell Mol Neurobiol.34(3) (2014), 437–449. doi:10.1007/s10571-014-0028-y.
20.
HyndM.R., ScottH.L. and DoddP.R., Selective loss of NMDA receptor NR1 subunit isoforms in Alzheimer's disease, J Neurochem.89(1) (2004), 240–247. doi:10.1111/j.1471-4159.2003.02330.x.
21.
InostrozaM., CidE., Brotons-MasJ., GalB., AivarP., UzcateguiY.G., SandiC. and Menendez de la PridaL., Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats, PLoS One.6(7) (2011), e22372. doi:10.1371/journal.pone.0022372.
22.
JaakoK., Aonurm-HelmA., KaldaA., AnierK., ZharkovskyT., ShastinD. and ZharkovskyA., Repeated citalopram administration counteracts kainic acid-induced spreading of PSA-NCAM-immunoreactive cells and loss of reelin in the adult mouse hippocampus, Eur J Pharmacol.666(1–3) (2011), 61–71. doi:10.1016/j.ejphar.2011.05.008.
23.
JinY., LimC.M., KimS.W., ParkJ.Y., SeoJ.-S., HanP.L., YoonS.H. and LeeJ.K., Fluoxetine attenuates kainic acid-induced neuronal cell death in the mouse hippocampus, Brain Res.1281 (2009), 108–116. doi:10.1016/j.brainres.2009.04.053.
KwanP. and BrodieM.J., Refractory epilepsy: Mechanisms and solutions, Expert Review of Neurotherapeutics6(3) (2006), 397–406. doi:10.1586/14737175.6.3.397.
26.
LeeJ., KimD., HongH., HanS. and KimJ., Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus, Neurosci Lett.286(3) (2000), 179–182. doi:10.1016/S0304-3940(00)01118-6.
27.
LeutgebS., LeutgebJ.K., BarnesC.A., MoserE.I., McNaughtonB.L. and MoserM.B., Independent codes for spatial and episodic memory in hippocampal neuronal ensembles, Science.309(5734) (2005), 619–623. doi:10.1126/science.1114037.
28.
LewerenzJ. and MaherP., Chronic glutamate toxicity in neurodegenerative diseases – What is the evidence?, Front Neurosci.9 (2015), 469.
29.
LiangL.P., BeaudoinM.E., FritzM.J., FultonR. and PatelM., Kainate-induced seizures, oxidative stress and neuronal loss in aging rats, Neuroscience.147(4) (2007), 1114–1118. doi:10.1016/j.neuroscience.2007.03.026.
30.
LiuG., KotloskiR.J. and McNamaraJ.O., Antiseizure effects of TrkB kinase inhibition, Epilepsia.55(8) (2014), 1264–1273. doi:10.1111/epi.12671.
31.
MachadoD.G., CunhaM.P., NeisV.B., BalenG.O., CollaA., BettioL.E., OliveiraA., PaziniF.L., DalmarcoJ.B., SimionattoE.L., PizzolattiM.G. and RodriguesA.L., Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L., Food Chem.136(2) (2013), 999–1005. doi:10.1016/j.foodchem.2012.09.028.
32.
MishraV., ShuaiB., KodaliM., ShettyG.A., HattiangadyB., RaoX. and ShettyA.K., Resveratrol treatment after status epilepticus restrains neurodegeneration and abnormal neurogenesis with suppression of oxidative stress and inflammation, Sci Rep.5 (2015), 17807. doi:10.1038/srep17807.
33.
MüllerC.J., GrötickeI., BankstahlM. and LöscherW., Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice, Exp Neurol.219(1) (2009), 284–297. doi:10.1016/j.expneurol.2009.05.035.
34.
ÖzcanM., Antioxidant activity of rosemary (Rosmarinus officinalis L.) extracts on natural olive and sesame oils, Grasas y Aceites.50(5) (1999), 355–358. doi:10.3989/gya.1999.v50.i5.679.
35.
PearsonJ.N., SchulzK.M. and PatelM., Specific alterations in the performance of learning and memory tasks in models of chemoconvulsant-induced status epilepticus, Epilepsy Res.108(6) (2014), 1032–1040. doi:10.1016/j.eplepsyres.2014.04.003.
36.
RacineR.J., Modification of seizure activity by electrical stimulation: I. After-discharge threshold, Electroencephalogr Clinical Neurophysiol.32(3) (1972), 269–279. doi:10.1016/0013-4694(72)90176-9.
37.
RamadanK.S., KhalilO.A., DanialE.N., AlnahdiH.S. and AyazN.O., Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats, J Physiol Biochem.69(4) (2013), 779–783. doi:10.1007/s13105-013-0253-8.
38.
RaškovićA., MilanovićI., PavlovićN., ĆebovićT., VukmirovićS. and MikovM., Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential, BMC Complement Altern Med.14 (2014), 225. doi:10.1186/1472-6882-14-225.
39.
RasoolijaziH., AzadN., JoghataeiM.T., KerdariM., NikbakhtF. and SoleimaniM., The protective role of carnosic acid against beta-amyloid toxicity in rats, Scientific World Journal.2013 (2013), 917082.
40.
RiljakV., MilotováM., JandováK., LangmeierM., MaresováD., PokornýJ. and TrojanS., Repeated kainic acid administration and hippocampal neuronal degeneration, Prague Med Rep.106(1) (2005), 75–78.
41.
SchmuedL.C. and HopkinsK.J., Fluoro-Jade: Novel fluorochromes for detecting toxicant-induced neuronal degeneration, Toxicol Pathol.28(1) (2000), 91–99. doi:10.1177/019262330002800111.
42.
SilvaR., FelicioL. and Frussa-FilhoR., Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice, Psychopharmacology (Berl)141(2) (1999), 111–117. doi:10.1007/s002130050814.
43.
Sotelo-FélixJ.I., Martinez-FongD., MurielP., SantillánR.L., CastilloD. and YahuacaP., Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat, J Ethnopharmacol.81(2) (2002), 145–154. doi:10.1016/S0378-8741(02)00090-9.
44.
SperkG., Kainic acid seizures in the rat, Prog Neurobiol.42(1) (1994), 1–32. doi:10.1016/0301-0082(94)90019-1.
45.
SperkG., LassmannH., BaranH., KishS.J., SeitelbergerF. and HornykiewiczO., Kainic acid induced seizures: Neurochemical and histopathological changes, Neuroscience.10(4) (1983), 1301–1315. doi:10.1016/0306-4522(83)90113-6.
46.
StafstromC.E., ThompsonJ.L. and HolmesG.L., Kainic acid seizures in the developing brain: Status epilepticus and spontaneous recurrent seizures, Brain Res Dev Brain Res.65(2) (1992), 227–236. doi:10.1016/0165-3806(92)90184-X.
47.
Stubley-WeatherlyL., HardingJ.W. and WrightJ.W., Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats, Brain Res.716(1–2) (1996), 29–38. doi:10.1016/0006-8993(95)01589-2.
48.
SunQ.J., DuanR.S., WangA.H., ShandW., ZhangT., ZhangX.Q. and ChiZ.F., Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits, Behav Brain Res.201(2) (2009), 292–299. doi:10.1016/j.bbr.2009.02.027.
49.
TripathiP.P., SantorufoG., BrilliE., BorrelliE. and BozziY., Kainic acid-induced seizures activate GSK-3β in the hippocampus of D2R-/- mice, Neuroreport.21(12) (2010), 846–850. doi:10.1097/WNR.0b013e32833d5891.
50.
WangQ., YuS., SimonyiA., SunG.Y. and SunA.Y., Kainic acid-mediated excitotoxicity as a model for neurodegeneration, Mol Neurobiol.31(1–3) (2005), 3–16.
51.
YoshiharaY., OnoderaH., IinumaK. and itoyamaY., Abnormal kainic acid receptor density and reduced seizure susceptibility in dystrophin-deficient mdx mice, Neuroscience117(2) (2003), 391–395. doi:10.1016/S0306-4522(02)00876-X.
52.
YoshiokaS., HamadaA., JobuK., YokotaJ., OnogawaM., KyotaniS., MiyamuraM., SaibaraT., OnishiS. and NishiokaY., Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis, J Pharm Pharmacol.62(2) (2010), 241–246. doi:10.1211/jpp.62.02.0012.
53.
ZeguraB., DobnikD., NiderlM.H. and FilipičM., Antioxidant and antigenotoxic effects of rosemary (Rosmarinus officinalis L.) extracts in Salmonella typhimurium TA98 and HepG2 cells, Environ Toxicol Pharmacol.32(2) (2011), 296–305. doi:10.1016/j.etap.2011.06.002.
