Changes in Nitric Oxide Synthesis and Epileptic Activity in the Contralateral Hippocampus of Rats Following Intrahippocampal Kainate Injection


Address correspondence and reprint requests to Dr. H. Yasuda at Department of Neurosurgery, Yamaguchi University School of Medicine 1144, Kogushi Ube, Yamaguchi 755-8505, Japan.


Summary:  Purpose: To investigate the effects of nitric oxide (NO) on seizure activity observed in brain areas that are remote from a primary epileptic focus.

Methods: Following an injection of kainate (concentration 1 mg/ml, volume 1 μl) in the rat hippocampus, we measured NO synthesis in the contralateral hippocampus and epileptic activity by electroencephalogram (EEG). The NO end products, nitrite and nitrate, were measured by in vivo microdialysis combined with an automated NO end-product analyzer and then used as indices of NO synthesis. We also assessed the effect of a specific inhibitor of neuronal NO synthase (NOS) on both the epileptic activity and NO synthesis in the contralateral hippocampus. For this assessment, we administered 7-nitroindazole (7-NI) (50 mg/kg) intraperitoneally 30 min before the kainate injection.

Results: Epileptic discharges in the contralateral hippocampus were frequently observed 90 min after unilateral hippocampus kainate injection. The duration of these discharges gradually increased until 240 min after the kainate injection. The NO end-product levels increased immediately after kainate injection and continued to increase gradually throughout the experiments, to a maximum of 213% of the base level. This elevation of NO end products was followed by epileptic discharges. Both the seizure activity and the elevation of contralateral hippocampus NO end-product levels were markedly attenuated in the animals that received 7-NI.

Conclusions: The results suggest that remote seizure activity caused by the transneuronal spread of kainate-induced discharges may be related to NO derived from neuronal NOS.