Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia

Abstract

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 mm 3, transgenic=27±13 mm 3, P=0.03; subcortex: wild type=33±14 mm 3, transgenic=23±10 mm 3, 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/100 g/min) was similar between groups (cortex: wild type=51±15 mm 3, transgenic=47±9 mm 3, P=0.65; subcortex: wild type=39±16 mm 3, transgenic=37±17 mm 3, 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.