CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy

The role of oxidative stress in seizure-induced brain injury was investigat ed in a kainic acid model of experimental epilepsy. Kainic acid (12.5 mg/kg ) or saline was injected intraperitoneally into 12-week-old male Fischer 34 4 rats and sacrificed by decapitation at 4 and 24 h after injection. Marker s of oxidative stress including protein carbonyls, thiobarbituric acid reac tive material (TBARs), glutathione (GSH) and glutathione disulfide (GSSG) w ere measured in hippocampus, cortex, cerebellum and basal ganglia. Four hou rs after treatment, protein carbonyls were elevated by 103, 55, 52 and 32% in cortex, hippocampus, basal ganglia and cerebellum, respectively. TBARs w ere increased by 30-45% in all areas. After 24 h, elevated protein and lipi d oxidative markers persisted in the hippocampus and cerebellum; by contras t, in the cortex, TBARs almost normalized to control values and protein car bonyls trended downward by one-half compared with measurements at 4 h, alth ough this reduction relative to the 4 h timepoint did not reach statistical significance. In the basal ganglia, protein carbonyls approached control v alues at 24 h. GSSG levels were only increased statistically in the cortex after 4 h. GSH levels in all the regions were unchanged after treatment wit h kainic acid. However, in cortex, GSH levels correlated negatively with in creases in protein and lipid oxidation (r = - 0.69, P < 0.002). In contrast , significant correlations between GSH, protein carbonyls and TBARs measure d in the hippocampus or cerebellum were not observed. Our data suggests tha t kainic acid induced similar oxidative stress in all of the brain regions that were examined, and that GSH plays a major antioxidant role in the cere bral cortex but not the hippocampus. (C) 2000 Elsevier Science B.V. All rig hts reserved.