MICE OVEREXPRESSING EXTRACELLULAR-SUPEROXIDE DISMUTASE HAVE INCREASEDRESISTANCE TO FOCAL CEREBRAL-ISCHEMIA

Transgenic mice, which had been transfected with the human extracellul ar superoxide dismutase gene, causing an approximate five-fold increas e in brain parenchymal extracellular superoxide dismutase activity, we re 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 in farct size were measured. Wild-type mice had larger infarcts (cortex: wild type= 37 +/- 14 mm(3), transgenic=27 +/- 13 mm(3) P=0.03; subcort ex: wild type=33 +/- 14 mm(3), transgenic=23+/-10mm(3), P=0.02). Neuro logical scores, however, were similar (P=0.29). Other mice underwent a utoradiographic determination of intra-ischemic cerebral blood flow. T he volume of tissue at risk of infarction (defined as volume of tissue where blood flow was <25ml/100 g/min) was similar between groups (cor tex: wild type = 51 +/- 15mm(3) transgenic=47 +/- 9 mm(3), P= 0.65; su bcortex: wild type= 39 +/- 16 mm(3), transgenic = 37 +/- 17 mm(3), P= 0.81). These results indicate that antioxidant scavenging of free radi cals by extracellular superoxide dismutase plays an important role in the histological response to a focal ischemic brain insult. (C) 1998 I BRO. Published by Elsevier Science Ltd.