Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia.
Transgenic mice, which had been transfected with the human extracellular superoxide dismutase gene, causing an approximate five-fold increase in brain parenchymal extracellular superoxide dismutase activity, were used to investigate the role of extracellular superoxide dismutase in ischemic brain injury. Transgenic (n = 21) and wild-type (n = 19) mice underwent 90 min of intraluminal middle cerebral artery occlusion and 24 h of reperfusion. Severity of resultant hemiparesis and cerebral infarct size were measured. Wild-type mice had larger infarcts (cortex: wild type =37+/-14 mm3, transgenic = 27+/-13 mm3, P=0.03; subcortex: wild type = 33+/-14 mm3, transgenic = 23+/-10 mm3, P = 0.02). Neurological scores, however, were similar (P = 0.29). Other mice underwent autoradiographic determination of intra-ischemic cerebral blood flow. The volume of tissue at risk of infarction (defined as volume of tissue where blood flow was <25 ml/100g/min) was similar between groups (cortex: wild type = 51+/-15 mm3, transgenic = 47+/-9 mm3, P=0.65; subcortex: wild type = 39+/-16 mm3, transgenic= 37+/-17 mm3, P=0.81). These results indicate that antioxidant scavenging of free radicals by extracellular superoxide dismutase plays an important role in the histological response to a focal ischemic brain insult.
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
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Sheng
R D
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Bart
T D
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Oury
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Pearlstein
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Crapo
D S
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Warner
D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D002941:Circle of Willis / Q000002:abnormalities / Q000033:anatomy & histology; D007839:Functional Laterality; D006400:Hematocrit; D006429:Hemiplegia / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D013482:Superoxide Dismutase