In vivo Evaluation of the Effect of Zonisamide on the Hippocampal Redox State During Kainic Acid-InducedSeizure Status in Rats

The aim in this study is to observe the hippocampal redox state during kainic-acid (KA)-induced seizure status, and examine the effect of systemic preinjection of anticonvulsant zonisamide (ZNS) on the hippocampal redox. To perform under a freely moving state, in vivo microdialysis method was applied to electron paramagnetic resonance (EPR) spectroscopy. Half-life of 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM), a five-membered ring nitroxide radical, was used for the indicator of the hippocampal antioxidant ability. The changes in EPR signal intensities of PCAM decreased exponentially in all rats used. The average half-lives of PCAM was significantly shorter in the rats pretreated with ZNS than that of control group, and while the average half-lives of PCAM in the perfusate was significantly longer in the rats KA-induced status epilepticus than that of control (P < 0.01). Those of PCAM in the ZNS-pretreated rats followed by KA-injection were almost the same as those of control. These findings indicate that the pretreatment of ZNS increased the antioxidant ability in the hippocampus during KA-induced seizure. This study is the first in vivo evaluation of the antioxidant ability of ZNS as neuroprotective role against the free radicals performed under the condition of freely moving rats during seizure status.