Neurologic deficits, memory loss, and histologic consequences of global cerebral ischemia in rats: Role of oxygen free-radical mediated reperfusion injury

This study assessed memory dysfunction and hippocampal cell loss in rats following a period of cerebral ischemia. The hypothesis that free radicals generated from xanthine oxidase at reperfusion mediate a substantial proportion of the injury following global cerebral ischemia was also studied.; Wistar rats were subjected to 10 minutes of carotid occlusion and hypotension using the two vessel-occlusion (2-VO) model. Neurologic tests were administered throughout the recovery period. Performance on a working memory task (discrete trial rewarded alternation) was evaluated beginning three weeks after surgery.; Following the ischemic episode, untreated rats displayed neurologic deficits and were impaired, compared to normal and sham-operated controls, on the test of working memory. The severity of the memory impairment correlated with neuronal damage in the CA1 field of the hippocampus. While scavenging the superoxide radical at the time of reperfusion with a highly specific scavenger, superoxide dismutase (SOD), significantly improved neurologic functions at the end of the first postoperative week, this difference failed to persist. Moreover, SOD treatment did not ameliorate either performance deficits on the memory test or cell loss in the hippocampus. Blocking free radical generation from xanthine oxidase with an enzymatic inhibitor, allopurinol, failed to produce any significant improvement.; These findings indicate that postischemic behavioral function correlates with histologic evidence of hippocampal injury. In this model, under these conditions, the proportion of free radical-mediated reperfusion injury appears to be small in comparison with the proportion of injury caused by the ischemia itself.