COPPER ZINC SUPEROXIDE-DISMUTASE TRANSGENIC BRAIN ACCUMULATES HYDROGEN-PEROXIDE AFTER PERINATAL HYPOXIA-ISCHEMIA/

Unlike the mature animal, immature mice transgenic for copper/zinc sup eroxide dismutase (SOD1) have greater brain injury after hypoxia-ische mia than their wild-type nontransgenic littermates. To assess the role of oxidative stress in the pathogenesis of this injury, we measured h istopathological damage, lipid peroxidation products, enzymatic activi ties of catalase and glutathione peroxidase, and hydrogen peroxide (H2 O2) concentration in these animals before and after hypoxic-ischemic i njury. Lipid peroxidation products were significantly increased 2 hour s after the insult in both transgenic and nontransgenic brains in hipp ocampus, the most damaged brain region. Catalase activity did not incr ease in response to SOD1 overexpression or injury in either group. How ever, glutathione peroxidase activity, unchanged in response to overex pression, decreased significantly 24 hours after injury in both groups . At 24 hours after injury, greater H2O2 accumulation was observed in transgenic brains. Because SOD1 dismutates superoxide to H2O2, overexp ression of SOD1 in the presence of developmentally low activities of t he catalytic enzymes glutathione peroxidase and catalase leads to an i ncreased production of H2O2, and may explain the increased brain injur y observed after hypoxia-ischemia in neonatal SOD1 mice.