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1、NIHPublicAccessAuthorManuscriptStroke.Authormanuscript;availableinPMC2009September1.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptStroke.2009March;40(3Suppl):S8±12.doi:10.1161/STROKEAHA.108.533166.AstrocytesandischemicinjuryTaka
2、hiroTakano,NancyAnnOberheim,MariaLuisaCotrina,andMaikenNedergaardDivisionofGlialDiseaseandTherapeutics.CenterforTranslationalNeuromedicine.DepartmentofNeurosurgery.UniversityofRochesterMedicalSchool.601ElmwoodAvenue,Rochester,NY14642AbstractIschemicinjuryistraditionallyviewedf
3、romanaxiomaticperspectiveofneuronalloss.Yettheischemicinfarctencompassesallcelltypes,includingastrocytes.Thisreviewwilldiscusstheideathatastrocytesplayafundamentalroleinthepathogenesisofischemicneuronaldeath.Itisproposedthatstrokeinjuryisprimarilyaconsequenceofthefailureofastr
4、ocytestosupporttheessentialmetabolicneedsofneurons.This‘gliocentricview’ofstrokeinjurypredictsthatpharmacologicalinterventionsspecificallytargetingneuronsareunlikelytosucceed,becauseitisnotfeasibletopreserveneuronalviabilityinanenvironmentthatfailstomeetessentialmetabolicrequi
5、rements.Neuroprotectiveeffortstargetingthefunctionalintegrityofastrocytesmayconstituteasuperiorstrategyforfutureneuroprotection.IntroductionOverthepastdecade,avirtualrevolutionhasoccurredinourunderstandingofthephysiologyofastrocytes,andoftheirinteractionswithneuronsinthenormal
6、brain1,2.Forexample,astrocytesactivelypropagateCa2+signalstoneighboringneurons,whoselevelofsynapticactivitytheycanactivelymodulate3,4.Keymediatorsofastrocyte-neuronsignalingareglutamate5andATP/adenosine6.Whilemuchcurrentworkisfocusedontheroleofgliotransmittersinsynaptictransmi
7、ssion,thepotentialharmfuleffectsofglutamate/ATPreleasefromastrocytesintheischemicpenumbrahasnotbeendefined.Also,astrocyteshaverecentlybeenimplicatedinthelocalcontrolofbloodflow7-9,butitisnotestablishedhowischemiaaffectstheabilityofastrocytestomodulatevasculartone.Wewillherecri
8、ticallyevaluateastrocytesasapotentialnewtherapeutictargetinst
