Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated Models of Immune Neuropathy 英文参考文献.docVIP

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Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated Models of Immune Neuropathy 英文参考文献.doc

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Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated Models of Immune Neuropathy 英文参考文献

ErythropoietinEnhancesNerveRepairinAnti- GangliosideAntibody-MediatedModelsofImmune Neuropathy GangZhang1,HelmarC.Lehmann2,NataliiaBogdanova1,TongGao1,JiangyangZhang3,KazimA. Sheikh1* 1Department of Neurology, University of Texas Medical School at Houston, Houston, Texas, United States of America, 2Department of Neurology, Heinrich-Heine- UniversityDu¨sseldorf,Du¨sseldorf,Germany,3DepartmentofRadiology,JohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica Abstract Guillain-Barre′ syndrome(GBS)isamonophasicimmuneneuropathicdisorderinwhichasignificantproportionofpatients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regenerationandtargetreinnervation.Anti-gangliosideantibodies(Abs)arethemostcommonlyrecognizedautoimmune markersinallformsofGBSandspecificAbsareassociatedwiththeslow/poorrecovery.Werecentlydemonstratedthat specificanti-gangliosideAbsinhibitaxonalregenerationandnerverepairinpreclinicalmodelsbyactivationofsmallGTPase RhoAanditsdownstreameffectors.Theobjectiveofthisstudywastodeterminewhethererythropoietin(EPO),apleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitoryeffectsofanti-gangliosideAbsonnerverepair.WefoundthatEPOcompletelyreversedtheinhibitoryeffectsof anti-gangliosideAbsonaxonregenerationincellculturemodelsandsignificantlyimprovednerveregeneration/repairinan animalmodel.Moreover,EPO-inducedproregenerativeeffectsinnervecellsarethroughEPOreceptorsandJanuskinase2/ Signaltransducerandactivatoroftranscription5pathwayandnotviaearlydirectmodulationofsmallGTPaseRhoA.These preclinicalstudiesindicatethatEPOisaviablecandidatedrugtodevelopfurtherforneuroprotectionandenhancingn