Abstracts

Aging is a major risk factor for developing status epilepticus and associated morbidity. The mechanisms underlying age-related increase in seizure susceptibility and resultant injury remain unknown. Oxidative stress is an important mechanism that contributes to diverse age-related pathologies. We have previously shown that chronic mitochondrial oxidative stress in Sod2-/+ mice renders them susceptible to age-related seizures and neuronal injury ([italic]Free Rad. Biol. Med. 36:542, 2004[/italic]). The goal of this study was determine if aging increases the susceptibility of rats to kainate-induced behavioral seizures and oxidative stress. Adult (4 month-old) and aging (18 month-old) Sprague-Dawley rats were administered either a single low dose of kainate or saline. Behavioral seizures were monitored in all four groups for a period of [sim]6 hr and oxidative stress parameters were assessed in the hippocampus 24 hr following kainate injection. Oxidative stress parameters were measured by spectrophotometry (mitochondrial aconitase inactivation) or HPLC-EC methods (8OhdG/2dG and GSH/GSSG ratios). In adult rats, administration of the low dose of kainate did not produce significant behavioral seizures or oxidative stress. However, 18 month-old rats exhibited intense behavioral seizures consistent with status epilepticus following the low dose of kainate. In 18 month-old rats, kainate produced a significant increase in hippocampal mitochondrial aconitase inactivation, oxidative DNA damage (8OhdG/2dG) and redox status (GSH/GSSG) compared to both age-matched controls and adult kainate-treated rats (2-way ANOVA, n=6 per group). These data suggest that the process of aging per se markedly increases kainate-induced seizure susceptibility and oxidative stress. (Supported by NINDS (RO1 NS039587).)