Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin‐specific T cell autoreactivity

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: oligodendrocyte progenitors;    myelination;    CD4 T cells;    periventricular leukomalacia;    motor function;   

DOI  :  10.1189/jlb.5HI0914-447R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

pCHisanimportantriskfactorforbraininjuryandlong‐termmorbidityinchildren,occurringduringthedevelopmentalstagesofneurogenesis,neuronalmigration,andmyelination.WeshowthatarodentmodelofpCHresultsinanearlydecreaseinmaturemyelin.AlthoughpCHdoesincreaseprogenitoroligodendrocytesinthedevelopingbrain,BrdUlabelingrevealedalossindividingprogenitoroligodendrocytes,indicatingadefectinmaturecellreplacementandmyelinogenesis.Micecontinuedtoexhibitedhypomyelination,concomitantwithlong‐termimpairmentofmotorfunction,weeksaftercessationofpCH.Theimplicationofanovelneuroimmunologicinterplay,pCHalsoinducedasignificantegressofinfiltratingCD4Tcellsintothedevelopingbrain.ThispCH‐mediatedneuroinflammationincludedoligodendrocyte‐directedautoimmunity,withanincreaseinperipheralmyelin‐specificCD4Tcells.Thus,boththelossofavailable,mature,myelin‐producingglialcellsandanactiveincreaseinautoreactive,myelin‐specificCD4TcellinfiltrationintopCHbrainsmaycontributetoearlypCH‐inducedhypomyelinationinthedevelopingCNS.Theelucidationofpotentialmechanismsofhypoxia‐drivenautoimmunitywillexpandourunderstandingoftheneuroimmuneaxisduringperinatalCNSdiseasestatesthatmaycontributetolong‐termfunctionaldisability...

【 授权许可】

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