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 mm(3), transgenic=27 +/- 13 mm(3) P=0.03; subcortex: wild type=33 +/- 14 mm(3), transgenic=23+/-10mm(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 <25ml/100 g/min) was similar between groups (cortex: wild type = 51 +/- 15mm(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. (C) 1998 IBRO. Published by Elsevier Science Ltd.