Reactive Astrocytes in Glial Scar Attract Olfactory Ensheathing Cells Migration by Secreted TNF-α in Spinal Cord Lesion of Rat 英文参考文献.docVIP

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Reactive Astrocytes in Glial Scar Attract Olfactory Ensheathing Cells Migration by Secreted TNF-α in Spinal Cord Lesion of Rat 英文参考文献.doc

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Reactive Astrocytes in Glial Scar Attract Olfactory Ensheathing Cells Migration by Secreted TNF-α in Spinal Cord Lesion of Rat 英文参考文献

ReactiveAstrocytesinGlialScarAttractOlfactory EnsheathingCellsMigrationbySecretedTNF-ainSpinal CordLesionofRat ZhidaSu,YiminYuan,JingjingChen,LiCao,YanlingZhu,LiangGao,YangQiu,ChengHe* InstituteofNeuroscienceandKeyLaboratoryofMolecularNeurobiologyofMinisterofEducation,NeuroscienceResearchCenterofChangzhengHospital,SecondMilitary MedicalUniversity,Shanghai,China Abstract Background: Afterspinalcordinjury (SCI),theformationofglialscarcontributestothefailure ofinjured adultaxonsto regeneratepastthelesion.Increasingevidenceindicatesthatolfactoryensheathingcells(OECs)implantedintospinalcord are found to migrate into the lesion site and induce axons regeneration beyond glial scar and resumption of functions. However,littleisknownaboutthemechanismsofOECsmigratingfrominjectionsitetoglialscar/lesionsite. MethodsandFindings:Inthepresentstudy,weidentifiedalinkbetweenOECsmigrationandreactiveastrocytesinglial scarthatwasmediatedbythetumornecrosisfactor-a(TNF-a).Initially,theBoydenchambermigrationassayshowedthat both glial scar tissue and reactive astrocyte-conditioned medium promoted OECs migration in vitro. Reactive astrocyte- derivedTNF-aanditstype1receptorTNFR1expressedonOECswereidentifiedtoberesponsibleforthepromotingeffect onOECsmigration.TNF-a-inducedOECsmigrationwasdemonstrateddependingonactivationoftheextracellularsignal- regulatedkinase(ERK)signalingcascades.Furthermore,TNF-asecretedbyreactiveastrocytesinglialscarwasalsoshowed toattractOECsmigrationinaspinalcordhemisectioninjurymodelofrat. Conclusions: These findings showed that TNF-a was released by reactive astrocytes in glial scar and attracted OECs migrationbyinteractingwithTNFR1expressedonOECsviaregulationofERKsignaling.Thismigration-attractingeffectof reactiveastrocytesonOECsmaysuggestamechanismforguidingOECsmigrationintoglialscar,whichiscrucialforOECs- mediatedaxonsregrowthbeyondthespinalcordlesionsite. Citation:SuZ,YuanY,ChenJ,CaoL,ZhuY,etal.(2009)ReactiveAstrocytesinGlialScarAttractOlfactoryEnsheathingC