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.