Kainic acid (KA) induces
seizures and degeneration in CA1 of the ventral hippocampus, though its mechanism of action is unknown. We used KA to induce
seizures in freely moving rats prepared for in vivo microdialysis with probe placement, and then measured extracellular
glutamate with an online fluorometric detector. Generation of
free radicals was monitored by electron paramagnetic resonance (EPR) spectroscopy coupled with perfusion of the spin-trapping agent, alpha-(4-pyridyl- N-oxide)- N- tert-butylnitrone (
POBN). Regional
antioxidant efficacy was measured by observing the eliminating ratio of
nitroxide radicals, using 3-carbamoyl-2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) applied exogenously from the probe. Increased levels of extracellular
glutamate observed at the initiation of KA-induced
seizures appear to be associated with generation of
lipid free radicals and with a decrease in residual
antioxidant effects. These data suggest that collapse of the redox state in the hippocampus, the region most vulnerable to injury from seizure activity, may be critical in the regional injury induced by
seizures. Further, we propose that the functional failure of
glutamate transporters due to oxidative stress results in high levels of extracellular
glutamate during sustained
generalized seizures induced with KA.