Abstracts

RATIONALE: We explored the hypothesis that seizure activity induced by kainate is associated with an oxidant injury by measuring F2-isoprostanes (F2-IsoPs), prostaglandin (PG)-like compounds generated by non-enzymatic free radical-catalyzed peroxidation of arachidonic acid.
METHODS: Formation of F2-IsoPs esterified in hippocampal subregion phospholipids, hippocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production were measured in the rat kainate model. F2-Isops were measured by mass spectrometry.
RESULTS: Neuronal loss was assessed 2 and 7 days post-kainate administration. In rats administered kainate (10 mg/kg, s.c.), neuronal loss was predominant in area CA3 2 days post-injection. Both CA3 and CA1 cell loss was observed 7 days following kainate administration, whereas the dentate gyrus (DG) showed minimal cell loss. F2-IsoPs were measured in microdissected hippocampal CA1, CA3 and DG 4, 8, 16, 24, 48 & 96 hr following kainate administration. Kainate administration induced a marked increase in F2-IsoP levels in the highly vulnerable CA3 region 16 hours post injection (3-fold ). The CA1 region showed small, but statistically insignificant increases in F2-IsoP levels. Interestingly, the DG, a region resistant to kainic acid-induced neuronal death also showed dramatic (3- to 5-fold) increases in F2-IsoP levels 8, 16, and 24 hours post injection. The increases in F2-Isop levels in CA3 and DG 16 hr post-injection were accompanied by inactivation of mitochondrial aconitase in these regions.
CONCLUSIONS: Utilizing F2-IsoP measurements has provided evidence for marked subregion-specific lipid peroxidation following kainic acid administration which suggests an important role for oxidant injury in seizure-induced excitotoxicity.
Support: Supported by Parents Against Childhood Epilepsy (PACE) and NIH RO1NS39587 to M.N.P.