Antioxidants, mitochondrial hyperoxidation and electrical recovery after anoxia in hippocampal slices

Cerebral injury may occur not only during brain ischemia but also during reperfusion afterward. A characteristic event during reperfusion after cerebral ischemia, or reoxygenation after anoxia in hippocampal slices, is hyperoxidation of the electron carriers of the mitochondrial respiratory chain. Earlier studies suggested that mitochondrial hyperoxidation was produced by an oxyradical mechanism and was linked to neuronal damage. Present studies sought to test this hypothesis by determining whether antioxidants could suppress mitochondrial hyperoxidation and improve electrical recovery after anoxia in hippocampal slices. Both 500 μM ascorbate and 50 μM glutathione decreased post-anoxic hyperoxidation of NADH and improved electrical recovery in hippocampal slices. These data support a role of oxygen free radicals in promoting post-anoxic mitochondrial hyperoxidation and electrical failure, and suggest that these effects of anoxia or ischemia may be linked.