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1、Proc.Natl.Acad.Sci.USAVol.88,pp.11158-11162,December1991NeurobiologyAttenuationoffocalcerebralischemicinjuryintransgenicmiceoverexpressingCuZnsuperoxidedismutase(middlecerebralarteryocclusion/brainedema/superoxideradicals)HIROYUKIKINOUCHI*,CHARLESJ.EPSTEINtt,TAKUJIMIZUI*,ELAINECARLSONt,SYLVIAF.C
2、HEN*,ANDPAKH.CHAN*§1Departmentsof*Neurology,§Neurosurgery,tPediatrics,and*BiochemistryandBiophysics,UniversityofCalifornia,SanFrancisco,CA94143CommunicatedbyJohnA.Clements,September16,1991(receivedforreviewJune28,1991)ABSTRACTOxygen-derivedfreeradicalshavebeenim-chemiainthegerbilbrain(13).Liposo
3、me-entrappedCuZn-plicatedinthepathogenesisofvasogenicedemaandinfarctionSOD,whichhasahalflifeof4.2hr(11),reducestheseveritycausedbyischeriaandreperfusioninjury.Inearlierstudies,oftraumaticandischemicinjuries(14,15).exogenouslysuppliedliposome-entrappedCuZnsuperoxideAlthoughthesestudiesprovidepote
4、ntialtherapeuticpre-dismutase(CuZn-SOD)amelioratedischemicbrainedemaandcedentsforthemanagementofbraininjury,alternativeinfarctioninratsfollowingfocalcerebralischemla.Toascer-experimentalapproachesareneededtoaddresstheissuesoftaindirectlytheroleofSODintheprotectionagainstsuper-theroleofoxygenfree
5、radicalsandthemodeofactionofSODoxideradical-inducedinjury,wemeasuredinfarctsizeandinischemicbraininjury.Toinvestigatedirectlytheroleofwatercontent24hrfollowingfocalcerebralischemiainincreasedbrainCuZn-SODinthepathogenesisofbrainnontransgenicmiceandintransgeicmicebearingthehumaninjuriespresumedto
6、involvesuperoxideradicals,wehaveSODIgene.Thesetransgenicmicehave3.1-foldhighercellularusedtransgenic(Tg)micecarryingthehumanCuZn-SODCuZn-SODactivityinthebrainthandotheirnontransgenicgene.ThesemicehaveincreasedlevelsofendogenousCuZn-littermates.Wealso'measuredantioxidantlevels(reducedSODactivityi
7、nbrainandotherorgans(16,17).Ouraiminglutathioneandreducedascorbate)ofcontralateralcortex,thisstudywastoexaminethehypothesisthatsuperoxideinfarctcortex,surroundingcortex,andstriatum.Infarctsizeradicalsplayaroleinthepathogenes
