Mitochondrial superoxide production in kainate-induced hippocampal damage

The objective of this study was to determine the role of mitochondrial supe roxide radical-mediated oxidative damage in seizure-induced neuronal death. Using aconitase inactivation as an index of superoxide production, we foun d that systemic administration of kainate in rats increased mitochondrial s uperoxide production in the hippocampus at times preceding neuronal death. 8-Hydroxy-2-deoxyguanosine, an oxidative lesion of DNA, was also increased in the rat hippocampus following kainate administration. Manganese(III) tet rakis(4-benzoic acid)porphyrin, a catalytic antioxidant, inhibited kainate- induced mitochondrial superoxide production, 8-hydroxy-2-deoxyguanosine for mation and neuronal loss in the rat hippocampus. Kainate-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were a ttenuated in transgenic mice overexpressing mitochondrial superoxide dismut ase-2. We propose that these results demonstrate a role for mitochondrial superoxi de production in hippocampal pathology produced by kainate seizures. (C) 20 00 IBRO. Published by Elsevier Science Ltd. All rights reserved.