Murine Neural StemProgenitor Cells Protect Neurons against Ischemia by HIF-1α–Regulated VEGF Signaling 英文参考文献.docVIP

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Murine Neural StemProgenitor Cells Protect Neurons against Ischemia by HIF-1α–Regulated VEGF Signaling 英文参考文献.doc

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Murine Neural StemProgenitor Cells Protect Neurons against Ischemia by HIF-1α–Regulated VEGF Signaling 英文参考文献

MurineNeuralStem/ProgenitorCellsProtectNeurons againstIschemiabyHIF-1a–RegulatedVEGFSignaling KateM.Harms,LuLi,LeeAnnaCunningham* DepartmentofNeurosciences,UniversityofNewMexicoHealthSciencesCenter,Albuquerque,NewMexico,UnitedStatesofAmerica Abstract Focalcerebralischemiafollowingmiddlecerebralarteryocclusion(MCAO)stimulatesarobustcytogenicresponsefromthe adult subventricular zone (SVZ) that includes massive proliferation of neural stem/progenitor cells (NSPCs) and cellular migrationintotheinjuryarea.TobegintoexplorebeneficialrolesofNSPCsinthisresponse,weinvestigatedtheabilityof embryonicandpostnatalNSPCstopromoteneuronalsurvivalunderconditionsofinvivoandinvitroischemia.Intracerebral transplantation of NSPCs attenuated neuronal apoptosis in response to focal ischemia induced by transient MCAO, and prevented neuronal cell death of cortical neurons in response to oxygen-glucose deprivation (OGD) in culture. NSPC- mediated neuroprotection was blocked by the pharmacological inhibitors of vascular endothelial growth factor (VEGF), SU1498 and Flt-1Fc. Embryonic and postnatal NSPCs were both intrinsically resistant to brief OGD exposure, and constitutively expressed both hypoxia-inducible factor 1a (HIF-1a) transcription factor and its downstream target, VEGF. Genomic deletion of HIF-1a by Cre-mediated excision of exon 2 in NSPC cultures resulted in .50% reduction of VEGF productionandablationofNSPC-mediatedneuroprotection.ThesefindingsindicatethatNSPCspromoteneuronalsurvival under ischemic conditions via HIF-1a-VEGF signaling pathways and support a role for NSPCs in promotion of neuronal survivalfollowingstroke. Citation: Harms KM, Li L, Cunningham LA (2010) Murine Neural Stem/Progenitor Cells Protect Neurons against Ischemia by HIF-1a–Regulated VEGF Signaling.PLoSONE5(3):e9767.doi:10.1371/journal.pone.0009767 Editor:RafaelLinden,UniversidadeFederaldoRiodeJaneiro(UFRJ),Brazil ReceivedDecember17,2009;AcceptedMarch3,2010;PublishedMarch22,2010 Copyright: ? 2010 Harms et al