Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus.
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.
Ueda
Yuto
Y
Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. usan@post1.miyazaki-med.ac.jp
Yokoyama
Hidekatsu
H
Nakajima
Akira
A
Tokumaru
Jun
J
Doi
Taku
T
Mitsuyama
Yoshio
Y
D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D005609:Free Radicals; D018698:Glutamic Acid; D007608:Kainic Acid