BRAIN INJURY AFTER PERINATAL HYPOXIA-ISCHEMIA IS EXACERBATED IN COPPER ZINC SUPEROXIDE-DISMUTASE TRANSGENIC MICE/

The role of superoxide radical formation in the pathogenesis of perina tal hypoxic-ischemic injury was examined using transgenic (Tg) mice ex pressing three times normal amounts of copper/zinc-superoxide dismutas e (CuZn/SOD). Fourteen litters of postnatal d 7 strain 218/3 mice were subjected to right common carotid artery ligation followed by 90 min of hypoxia in an 8% oxygen/humidified chamber maintained at 37 degrees C. Both Tg mice (n = 32) and their nontransgenic (nTg) littermates (n = 30) survived the injury equally. Evaluation of infarcted brain area s measured by video image analysis of three coronal brain sections thr ough the anterior hippocampus from each animal revealed that the Tg an imals suffered brain infarction more frequently than did nTg mice, Bli nded histologic scoring of cerebral cortex and striatum 5 d after inju ry revealed that Tg mice were more likely to have higher histologic se verity scores than their nTg littermates (p = 0.0463, Mann-Whitney U t est). These findings suggest that brain injury in perinatal hypoxia-is chemia may be mediated in part by free radical formation from excessiv e hydrogen peroxide or nitric oxide production.