In civilian and military settings, mild traumatic brain injury (mTBI) is a common consequence of impacts to the head, sudden blows to the body, and exposure to high-energy atmospheric shockwaves from blast. In some cases, mTBI from blast exposure results in long-term emotional and cognitive deficits and an elevated risk for certain neuropsychiatric diseases. Here, we tested the effects of mTBI on various forms of auditory-cued fear learning and other measures of cognition in male C57BL/6J mice after single or repeated blast exposure (blast TBI; bTBI). bTBI produced an abnormality in the temporal organization of cue-induced freezing behavior in a conditioned trace fear test. Spatial working memory, evaluated by the Y-maze task performance, was also deleteriously affected by bTBI. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis for glial markers indicated an alteration in the expression of myelin-related genes in the hippocampus and corpus callosum 1–8 weeks after bTBI. Immunohistochemical and ultrastructural analyses detected bTBI-related myelin and axonal damage in the hippocampus and corpus callosum. Together, these data suggest a possible link between blast-induced mTBI, myelin/axonal injury, and cognitive dysfunction.
Get full access to this article
View all access options for this article.
References
1.
DewanM.C., RattaniA., GuptaS., BaticulonR.E., HungY.C., PunchakM., AgrawalA., AdeleyeA.O., ShrimeM.G., RubianoA.M., RosenfeldJ.V., and ParkK.B. (2018). Estimating the global incidence of traumatic brain injury. J. Neurosurg. doi: 10.3171/2017.10.JNS17352.
2.
G.B.D. Traumatic Brain Injury and Spinal Cord Injury Collaborators. (2019). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 56–87.
3.
KontosA.P., ElbinR.J., KotwalR.S., LutzR.H., KaneS., BensonP.J., ForstenR.D., and CollinsM.W. (2015). The effects of combat-related mild traumatic brain injury (mTBI): does blast mTBI history matter?. J. Trauma Acute Care Surg. 79, 4 Suppl. 2, S146–S151.
4.
MendezM.F., OwensE.M., JimenezE.E., PeppersD., and LichtE.A. (2013). Changes in personality after mild traumatic brain injury from primary blast vs. blunt forces. Brain Inj. 27, 10–18.
5.
MendezM.F., OwensE.M., Reza BerenjiG., PeppersD.C., LiangL.J., and LichtE.A. (2013). Mild traumatic brain injury from primary blast vs. blunt forces: post-concussion consequences and functional neuroimaging. NeuroRehabilitation, 32, 397–407.
6.
IvanovI., FernandezC., MitsisE.M., DicksteinD.L., WongE., TangC.Y., SimantovJ., BangC., MoshierE., SanoM., ElderG.A., and HazlettE.A. (2017). Blast exposure, white matter integrity, and cognitive function in Iraq and Afghanistan combat veterans. Front. Neurol. 8, 127.
7.
LindquistL.K., LoveH.C., and ElbogenE.B. (2017). Traumatic brain injury in Iraq and Afghanistan veterans: new results from a national random sample study. J. Neuropsychiatry Clin. Neurosci. 29, 254–259.
8.
KovacsS.K., LeonessaF., and LingG.S. (2014). Blast TBI models, neuropathology, and implications for seizure risk. Front. Neurol. 5, 47.
9.
KatzE., OfekB., AdlerJ., AbramowitzH.B., and KrauszM.M. (1989). Primary blast injury after a bomb explosion in a civilian bus. Ann. Surg. 209, 484–488.
10.
SinghA.K., DitkofskyN.G., YorkJ.D., AbujudehH.H., AveryL.A., BrunnerJ.F., SodicksonA.D., and LevM.H. (2016). Blast injuries: from improvised explosive device blasts to the Boston Marathon bombing. Radiographics, 36, 295–307.
11.
XiongY., MahmoodA., and ChoppM. (2013). Animal models of traumatic brain injury. Nat. Rev. Neurosci. 14, 128–142.
TaberK.H., WardenD.L., and HurleyR.A. (2006). Blast-related traumatic brain injury: what is known?. J. Neuropsychiatry Clin. Neurosci. 18, 141–145.
14.
FievisohnE., BaileyZ., GuettlerA., and VandeVordP. (2018). Primary blast brain injury mechanisms: current knowledge, limitations, and future directions. J. Biomech. Eng. 140. doi: 10.1115/1.4038710.
15.
VuP.A., TuckerL.B., LiuJ., McNamaraE.H., TranT., FuA.H., KimY., and McCabeJ.T. (2018). Transient disruption of mouse home cage activities and assessment of orexin immunoreactivity following concussive- or blast-induced brain injury. Brain Res. 1700, 138–151.
16.
LeonardiA.D., BirC.A., RitzelD.V. and VandeVordP.J. (2011). Intracranial pressure increases during exposure to a shock wave. J Neurotrauma, 28, 85–94.
17.
SawyerT.W., WangY., RitzelD.V., JoseyT., VillanuevaM., SheiY., NelsonP., HennesG., WeissT., VairC., FanC., and BarnesJ. (2016). High-fidelity simulation of primary blast: direct effects on the head. J. Neurotrauma, 33, 1181–1193.
18.
CernakI. (2015). Blast injuries and blast-induced neurotrauma: overview of pathophysiology and experimental knowledge models and findings, in: Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. E.H. Kobeissy (ed). CRC/Taylor & Francis;: Boca Raton,FL.
19.
LongJ.B., BentleyT.L., WessnerK.A., CeroneC., SweeneyS., and BaumanR.A. (2009). Blast overpressure in rats: recreating a battlefield injury in the laboratory. J. Neurotrauma, 26, 827–840.
20.
KoliatsosV.E., CernakI., XuL., SongY., SavonenkoA., CrainB.J., EberhartC.G., FrangakisC.E., MelnikovaT., KimH., and LeeD. (2011). A mouse model of blast injury to brain: initial pathological, neuropathological, and behavioral characterization. J. Neuropathol. Exp. Neurol. 70, 399–416.
21.
CernakI., O'ConnorC. and VinkR. (2001). Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats. Clin. Exp. Pharmacol. Physiol. 28, 922–925.
22.
SaljoA., SvenssonB., MayorgaM., HambergerA., and BolouriH. (2009). Low-level blasts raise intracranial pressure and impair cognitive function in rats. J. Neurotrauma, 26, 1345–1352.
23.
MuelblM.J., SlakerM.L., ShahA.S., NawarawongN.N., GerndtC.H., BuddeM.D., StemperB.D., and OlsenC.M. (2018). Effects of mild blast traumatic brain injury on cognitive- and addiction-related behaviors. Sci. Rep. 8, 9941.
24.
GenoveseR.F., SimmonsL.P., AhlersS.T., Maudlin-JeronimoE., DaveJ.R., and BoutteA.M. (2013). Effects of mild TBI from repeated blast overpressure on the expression and extinction of conditioned fear in rats. Neuroscience, 254, 120–129.
25.
ElderG.A., DorrN.P., De GasperiR., Gama SosaM.A., ShaughnessM.C., Maudlin-JeronimoE., HallA.A., McCarronR.M., and AhlersS.T. (2012). Blast exposure induces post-traumatic stress disorder-related traits in a rat model of mild traumatic brain injury. J. Neurotrauma, 29, 2564–2575.
26.
Perez-GarciaG., Gama SosaM.A., De GasperiR., TschiffelyA.E., McCarronR.M., HofP.R., GandyS., AhlersS.T., and ElderG.A. (2019). Blast-induced “PTSD”: evidence from an animal model. Neuropharmacology, 145, 220–229.
27.
BelangerH.G., KretzmerT., Yoash-GantzR., PickettT., and TuplerL.A. (2009). Cognitive sequelae of blast-related versus other mechanisms of brain trauma. J. Int. Neuropsychol. Soc. 15, 1–8.
28.
SchwartzI., TuchnerM., TsenterJ., ShochinaM., ShoshanY., Katz-LeurerM., and MeinerZ. (2008). Cognitive and functional outcomes of terror victims who suffered from traumatic brain injury. Brain Inj. 22, 255–263.
29.
YurgilK.A., BarkauskasD.A., VasterlingJ.J., NievergeltC.M., LarsonG.E., SchorkN.J., LitzB.T., NashW.P., and BakerD.G.; Marine Resiliency StudyTeam. (2014). Association between traumatic brain injury and risk of posttraumatic stress disorder in active-duty Marines. JAMA Psychiatry, 71, 149–157.
30.
WallP.L. (2012). Posttraumatic stress disorder and traumatic brain injury in current military populations: a critical analysis. J. Am. Psychiatr. Nurses Assoc. 18, 278–298.
31.
SchneidermanA.I., BraverE.R., and KangH.K. (2008). Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent postconcussive symptoms and posttraumatic stress disorder. Am. J. Epidemiol. 167, 1446–1452.
32.
JorgeR.E., AcionL., WhiteT., Tordesillas-GutierrezD., PiersonR., Crespo-FacorroB., and MagnottaV.A. (2012). White matter abnormalities in veterans with mild traumatic brain injury. Am. J. Psychiatry, 169, 1284–1291.
33.
DennisE.L., WildeE.A., NewsomeM.R., ScheibelR.S., TroyanskayaM., VelezC., WadeB.S.C., DrennonA.M., YorkG.E., BiglerE.D., AbildskovT.J., TaylorB.A., JaramilloC.A., EapenB., BelangerH., GuptaV., MoreyR., HaswellC., LevinH.S., HindsS.R., 2nd, WalkerW.C., ThompsonP.M., and TateD.F. (2018). Enigma military brain injury: a coordinated meta-analysis of diffusion MRI from multiple cohorts. Proc. IEEE Int. Symp. Biomed. Imaging, 2018, 1386–1389.
34.
TaberK.H., HurleyR.A., HaswellC.C., RowlandJ.A., HurtS.D., LamarC.D., and MoreyR.A. (2015). White matter compromise in veterans exposed to primary blast forces. J. Head Trauma Rehabil. 30, E15–E25.
35.
DavenportN.D., LimK.O., ArmstrongM.T., and SponheimS.R. (2012). Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury. NeuroImage, 59, 2017–2024.
MillerD.R., HayesJ.P., LaflecheG., SalatD.H., and VerfaellieM. (2016). White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury. Hum. Brain Mapp. 37, 220–229.
38.
Mac DonaldC.L., BarberJ., AndreJ., EvansN., PanksC., SunS., ZalewskiK., Elizabeth SandersR., and TemkinN. (2017). 5-Year imaging sequelae of concussive blast injury and relation to early clinical outcome. NeuroImage Clin. 14, 371–378.
39.
RitzelD.V., ParksS.A., RoseveareJ., RudeG., and SawyerT.W. (2011). Experimental blast simulation for injury studies. Presented at the RTO Human Factors and Medicine Panel (HFM) Symposium, NATO Science and Technology Organization, Halifax, Nova Scotia, Canada.
BukaloO., PinardC.R., SilversteinS., BrehmC., HartleyN.D., WhittleN., ColaciccoG., BuschE., PatelS., SingewaldN., and HolmesA. (2015). Prefrontal inputs to the amygdala instruct fear extinction memory formation. Sci. Adv. 1, e1500251.
42.
BukaloO., NonakaM., WeinholtzC.A., MendezA., TaylorW.W., and HolmesA. (2021). Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction. Behav. Brain Res. 396, 112913.
43.
Gunduz-CinarO., BrockwayE., LederleL., WilcoxT., HalladayL.R., DingY., OhH., BuschE.F., KaugarsK., FlynnS., LimogesA., BukaloO., MacPhersonK.P., MasneufS., PinardC., SibilleE., CheslerE.J., and HolmesA. (2019). Identification of a novel gene regulating amygdala-mediated fear extinction. Mol. Psychiatry, 24, 601–612.
44.
BrigmanJ.L., WrightT., TalaniG., Prasad-MulcareS., JindeS., SeaboldG.K., MathurP., DavisM.I., BockR., GustinR.M., ColbranR.J., AlvarezV.A., NakazawaK., DelpireE., LovingerD.M., and HolmesA. (2010). Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning. J. Neurosci. 30, 4590–4600.
45.
FeyderM., WiedholzL., SprengelR., and HolmesA. (2007). Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors. Front. Behav. Neurosci. 1, 4.
46.
KoganJ.H., FranklandP.W., and SilvaA.J. (2000). Long-term memory underlying hippocampus-dependent social recognition in mice. Hippocampus, 10, 47–56.
47.
SandersonD.J., GoodM.A., SkeltonK., SprengelR., SeeburgP.H., RawlinsJ.N., and BannermanD.M. (2009). Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model. Learn. Mem. 16, 379–386.
48.
Arancibia-CarcamoI.L., FordM.C., CossellL., IshidaK., TohyamaK., and AttwellD. (2017). Node of Ranvier length as a potential regulator of myelinated axon conduction speed. Elife, 6, e23329.
49.
FranklinK.B.J., and PaxinosG. (2001). The Mouse Brain in Stereotaxic Coordinates, 2nd ed. Academic: London.
50.
SchindelinJ., Arganda-CarrerasI., FriseE., KaynigV., LongairM., PietzschT., PreibischS., RuedenC., SaalfeldS., SchmidB., TinevezJ.Y., WhiteD.J., HartensteinV., EliceiriK., TomancakP., and CardonaA. (2012). Fiji: an open-source platform for biological-image analysis. Nat. Methods, 9, 676–682.
51.
BakerW.E. (1973). Explosions in the Air. University of Texas Press: Austin, TX.
52.
WeissC., LendackiF.R., RigbyP.H., WyrwiczA.M., DisterhoftJ.F., and SpiessJ. (2020). Conditioned contextual freezing is a neurobehavioral biomarker of axonal injury indicated by reduced fractional anisotropy in a mouse model of blast-induced mild traumatic brain injury. Shock, 53, 744–753.
53.
BelangerH.G., Proctor-WeberZ., KretzmerT., KimM., FrenchL.M., and VanderploegR.D. (2011). Symptom complaints following reports of blast versus non-blast mild TBI: does mechanism of injury matter?. Clin. Neuropsychol. 25, 702–715.
54.
HanC.J., O'TuathaighC.M., van TrigtL., QuinnJ.J., FanselowM.S., MongeauR., KochC., and AndersonD.J. (2003). Trace but not delay fear conditioning requires attention and the anterior cingulate cortex. Proc. Natl. Acad. Sci. U. S. A. 100, 13087–13092.
55.
McEchronM.D., BouwmeesterH., TsengW., WeissC., and DisterhoftJ.F. (1998). Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat. Hippocampus, 8, 638–646.
56.
BurmanM.A., SimmonsC.A., HughesM., and LeiL. (2014). Developing and validating trace fear conditioning protocols in C57BL/6 mice. J. Neurosci. Methods, 222, 111–117.
57.
HuertaP.T., SunL.D., WilsonM.A., and TonegawaS. (2000). Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron, 25, 473–480.
58.
RegerM.L., PoulosA.M., BuenF., GizaC.C., HovdaD.A., and FanselowM.S. (2012). Concussive brain injury enhances fear learning and excitatory processes in the amygdala. Biol. Psychiatry, 71, 335–343.
59.
SeoD.O., CarilloM.A., Chih-Hsiung LimS., TanakaK.F., and DrewM.R. (2015). Adult hippocampal neurogenesis modulates fear learning through associative and nonassociative mechanisms. J. Neurosci. 35, 11330–11345.
60.
BekkuY., VargovaL., GotoY., VorisekI., DmytrenkoL., NarasakiM., OhtsukaA., FasslerR., NinomiyaY., SykovaE., and OohashiT. (2010). Bral1: its role in diffusion barrier formation and conduction velocity in the CNS. J. Neurosci. 30, 3113–3123.
61.
TrappB.D., BernierL., AndrewsS.B., and ColmanD.R. (1988). Cellular and subcellular distribution of 2′,3′-cyclic nucleotide 3′-phosphodiesterase and its mRNA in the rat central nervous system. J. Neurochem. 51, 859-868.
62.
MarinelliC., BertalotT., ZussoM., SkaperS.D., and GiustiP. (2016). Systematic review of pharmacological properties of the oligodendrocyte lineage. Front. Cell. Neurosci. 10, 27.
63.
AggarwalS., YurlovaL., SnaideroN., ReetzC., FreyS., ZimmermannJ., PahlerG., JanshoffA., FriedrichsJ., MullerD.J., GoebelC., and SimonsM. (2011). A size barrier limits protein diffusion at the cell surface to generate lipid-rich myelin-membrane sheets. Dev. Cell, 21, 445–456.
64.
CaldwellJ.H., SchallerK.L., LasherR.S., PelesE., and LevinsonS.R. (2000). Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc. Natl. Acad. Sci. U. S. A. 97, 5616–5620.
65.
HayesJ.P., BiglerE.D., and VerfaellieM. (2016). Traumatic brain injury as a disorder of brain connectivity. J. Int. Neuropsychol. Soc. 22, 120–137.
66.
RosenbluthJ. (1966). Redundant myelin sheaths and other ultrastructural features of the toad cerebellum. J. Cell Biol. 28, 73–93.
67.
MierzwaA.J., MarionC.M., SullivanG.M., McDanielD.P., and ArmstrongR.C. (2015). Components of myelin damage and repair in the progression of white matter pathology after mild traumatic brain injury. J. Neuropathol. Exp. Neurol. 74, 218–232.
68.
Sierra-MercadoD., McAllisterL.M., LeeC.C., MiladM.R., EskandarE.N., and WhalenM.J. (2015). Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice. Brain Res. 1606, 133–141.
69.
CorneR., LeconteC., OuradouM., FassinaV., ZhuY., DeouE., BessonV., PlotkineM., Marchand-LerouxC., and MongeauR. (2019). Spontaneous resurgence of conditioned fear weeks after successful extinction in brain injured mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 88, 276–286.
70.
HeldtS.A., ElbergerA.J., DengY., GuleyN.H., Del MarN., RogersJ., ChoiG.W., FerrellJ., RexT.S., HonigM.G., and ReinerA. (2014). A novel closed-head model of mild traumatic brain injury caused by primary overpressure blast to the cranium produces sustained emotional deficits in mice. Front. Neurol. 5, 2.
71.
Perez GarciaG., PerezG.M., De GasperiR., Gama SosaM.A., Otero-PaganA., PryorD., AbutarboushR., KawoosU., HofP., CookD., GandyS.E., AhlersS., and ElderG.A. (2021). Progressive cognitive and PTSD-related behavioral traits in rats exposed to repetitive low-level blast. J. Neurotrauma. doi: 10.1089/neu.2020.7398.
72.
Perez-GarciaG., Gama SosaM.A., De GasperiR., Lashof-SullivanM., Maudlin-JeronimoE., StoneJ.R., HaghighiF., AhlersS.T., and ElderG.A. (2018). Chronic post-traumatic stress disorder-related traits in a rat model of low-level blast exposure. Behav. Brain Res. 340, 117–125.
73.
Perez-GarciaG., De GasperiR., Gama SosaM.A., PerezG.M., Otero-PaganA., TschiffelyA., McCarronR.M., AhlersS.T., ElderG.A., and GandyS. (2018). PTSD-related behavioral traits in a rat model of blast-induced mTBI are reversed by the mGluR2/3 receptor antagonist BCI-838. eNeuro, 5, ENEURO.0357-17.2018.
74.
RatliffW.A., MervisR.F., CitronB.A., SchwartzB., RubovitchV., SchreiberS., and PickC.G. (2019). Mild blast-related TBI in a mouse model alters amygdalar neurostructure and circuitry. Exp. Neurol. 315, 9–14.
75.
BuW., RenH., DengY., Del MarN., GuleyN.M., MooreB.M., HonigM.G., and ReinerA. (2016). Mild traumatic brain injury produces neuron loss that can be rescued by modulating microglial activation using a CB2 receptor inverse agonist. Front. Neurosci. 10, 449.
76.
BlazeJ., ChoiI., WangZ., UmaliM., MendelevN., TschiffelyA.E., AhlersS.T., ElderG.A., GeY., and HaghighiF. (2020). Blast-related mild TBI alters anxiety-like behavior and transcriptional signatures in the rat amygdala. Front. Behav. Neurosci. 14, 160.
77.
SingewaldN., and HolmesA. (2019). Rodent models of impaired fear extinction. Psychopharmacology (Berl.) 236, 21–32.
78.
TovoteP., FadokJ.P., and LuthiA. (2015). Neuronal circuits for fear and anxiety. Nat. Rev. Neurosci. 16, 317–331.
79.
AravindA., RavulaA.R., ChandraN., and PfisterB.J. (2020). Behavioral deficits in animal models of blast traumatic brain injury. Front. Neurol. 11, 990.
80.
KaplanG.B., Leite-MorrisK.A., WangL., RumbikaK.K., HeinrichsS.C., ZengX., WuL., ArenaD.T., and TengY.D. (2018). Pathophysiological bases of comorbidity: traumatic brain injury and post-traumatic stress disorder. J. Neurotrauma, 35, 210–225.
81.
DuttaD.J., WooD.H., LeeP.R., PajevicS., BukaloO., HuffmanW.C., WakeH., BasserP.J., SheikhBahaeiS., LazarevicV., SmithJ.C., and FieldsR.D. (2018). Regulation of myelin structure and conduction velocity by perinodal astrocytes. Proc. Natl. Acad. Sci. U. S. A. 115, 11832–11837.
82.
FieldsR.D. (2008). White matter in learning, cognition and psychiatric disorders. Trends Neurosci. 31, 361–370.
83.
AuerF., VagionitisS., and CzopkaT. (2018). Evidence for myelin sheath remodeling in the CNS revealed by in vivo imaging. Curr. Biol. 28, 549–559.e3.
84.
HildebrandC., MustafaG.Y., and WaxmanS.G. (1986). Remodelling of internodes in regenerated rat sciatic nerve: electron microscopic observations. J. Neurocytol. 15, 681–692.
85.
MarionC.M., RadomskiK.L., CramerN.P., GaldzickiZ., and ArmstrongR.C. (2018). Experimental traumatic brain injury identifies distinct early and late phase axonal conduction deficits of white matter pathophysiology, and reveals intervening recovery. J. Neurosci. 38, 8723–8736.
86.
MiyataS., TaniguchiM., KoyamaY., ShimizuS., TanakaT., YasunoF., YamamotoA., IidaH., KudoT., KatayamaT., and TohyamaM. (2016). Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression. Sci. Rep. 6, 23084.
87.
BarakB., ZhangZ., LiuY., NirA., TrangleS.S., EnnisM., LevandowskiK.M., WangD., QuastK., BoultingG.L., LiY., BayarsaihanD., HeZ., and FengG. (2019). Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug. Nat. Neurosci. 22, 700–708.
88.
SilvaA.I., HaddonJ.E., Ahmed SyedY., TrentS., LinT.E., PatelY., CarterJ., HaanN., HoneyR.C., HumbyT., AssafY., OwenM.J., LindenD.E.J., HallJ., and WilkinsonL.S. (2019). Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility. Nat. Commun. 10, 3455.
89.
PanS., MayoralS.R., ChoiH.S., ChanJ.R., and KheirbekM.A. (2020). Preservation of a remote fear memory requires new myelin formation. Nat. Neurosci. 23, 487–499.
90.
WangF., RenS.Y., ChenJ.F., LiuK., LiR.X., LiZ.F., HuB., NiuJ.Q., XiaoL., ChanJ.R., and MeiF. (2020). Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory. Nat. Neurosci. 23, 481–486.
91.
SteadmanP.E., XiaF., AhmedM., MocleA.J., PenningA.R.A., GeraghtyA.C., SteenlandH.W., MonjeM., JosselynS.A., and FranklandP.W. (2020). Disruption of oligodendrogenesis impairs memory consolidation in adult mice. Neuron, 105, 150–164.e6.
92.
NawarawongN.N., SlakerM., MuelblM., ShahA.S., ChiarielloR., NelsonL.D., BuddeM.D., StemperB.D., and OlsenC.M. (2019). Repeated blast model of mild traumatic brain injury alters oxycodone self-administration and drug seeking. Eur. J. Neurosci. 50, 2101–2112.
93.
BugayV., BozdemirE., VigilF.A., ChunS.H., HolsteinD.M., ElliottW.R., SpragueC.J., CavazosJ.E., ZamoraD.O., RuleG., ShapiroM.S., LechleiterJ.D., and BrennerR. (2020). A mouse model of repetitive blast traumatic brain injury reveals post-trauma seizures and increased neuronal excitability. J. Neurotrauma, 37, 248–261.
94.
CalabreseE., DuF., GarmanR.H., JohnsonG.A., RiccioC., TongL.C., and LongJ.B. (2014). Diffusion tensor imaging reveals white matter injury in a rat model of repetitive blast-induced traumatic brain injury. J. Neurotrauma, 31, 938–950.
95.
BadeaA., KamnakshA., AndersonR.J., CalabreseE., LongJ.B., and AgostonD.V. (2018). Repeated mild blast exposure in young adult rats results in dynamic and persistent microstructural changes in the brain. NeuroImage Clin. 18, 60–73.
GreenA.J., GelfandJ.M., CreeB.A., BevanC., BoscardinW.J., MeiF., InmanJ., ArnowS., DevereuxM., AbounasrA., NobutaH., ZhuA., FriessenM., GeronaR., von BudingenH.C., HenryR.G., HauserS.L., and ChanJ.R. (2017). Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet, 390, 2481–2489.
98.
HublerZ., AllimuthuD., BedermanI., ElittM.S., MadhavanM., AllanK.C., ShickH.E., GarrisonE., M, T.K., FactorD.C., NevinZ.S., SaxJ.L., ThompsonM.A., FedorovY., JinJ., WilsonW.K., GieraM., BracherF., MillerR.H., TesarP.J., and AdamsD.J. (2018). Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature, 560, 372–376.
99.
WelliverR.R., PolancoJ.J., SeidmanR.A., SinhaA.K., O'BaraM.A., KhakuZ.M., Santiago GonzalezD.A., NishiyamaA., WessJ., FeltriM.L., PaezP.M., and SimF.J. (2018). Muscarinic receptor M3R signaling prevents efficient remyelination by human and mouse oligodendrocyte progenitor cells. J. Neurosci. 38, 6921–6932.
100.
SangobowaleM., NikulinaE., and BergoldP.J. (2018). Minocycline plus N-acetylcysteine protect oligodendrocytes when first dosed 12 hours after closed head injury in mice. Neurosci. Lett. 682, 16–20.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
