Enhanced hippocampal F-2-isoprostane formation following kainate-induced seizures

We attempted to obtain evidence for the occurrence of oxidant injury follow ing seizure activity by measuring hippocampal F-2-isoprostanes (F-2-IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F-2-IsoPs esterified in hippocampal phospholipids was correlated with hipp ocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production in the kainate model. F-2-IsoPs were measured in mic rodissected hippocampal CAI, CA3 and dentate gyrus (DG) regions at various times following kainate administration. Kainate produced a large increase i n F-2-IsoP levels in the highly vulnerable CA3 region 16 h post injection. The CAI region showed small, but statistically insignificant increases in F -2-IsoP levels. Interestingly, the DG, a region resistant to kainate-induce d neuronal death also showed marked (2.5-5-fold) increases in F-2-IsoP leve ls 8, 16, and 24 h post injection. The increases in F-2-Isop levels in CA3 and DG were accompanied by inactivation of mitochondrial aconitase in these regions. This marked subregion-specific increase in F-2-Isop following kai nate administration suggests that oxidative lipid damage results from seizu re activity and may play an important role in seizure-induced death of vuln erable neurons.