Abstracts

Rationale: Kindling is a widely used animal model of intractable temporal lobe epilepsy. We have performed spectral analysis on the afterdischarge (AD) induced by chronic hippocampal kindling of the rabbit and revealed that enhancement of the higher frequency band (HFB: 12-30 Hz) component is associated with kindled stage, while decrement of it is associated with incomplete kindling stage (Tsuchiya et al., Epilepsy Res, 2011; 2012). Meanwhile, we previously demonstrated that the Ih blockers CsCl and ZD7288 can significantly increase the threshold of electrically induced paroxysmal discharge in the rabbit hippocampus (Kitayama et al., Epilepsia, 2003). However, the role of Ih channel in epileptogenesis is controversial. In the present study, we examined the effects of ZD7288 on ADs induced by acute kindling of the rabbit hippocampus to reveal the contribution of Ih channel in epileptogenesis with using spectral analysis. Methods: We performed all experiments under appropriate conditions in accordance with the Declaration of Helsinki and the Guide for Animal Experimentation at Soka University. Seven adult rabbits were used. Under deeply anesthesia, we delivered acutely kindling stimulation (1 ms biphasic pulses, 50 Hz, 1 s) with suprathreshold intensity for AD at 20-min intervals to the right hippocampus. Kindling stimulations were performed at least 30 times unless spectral changes occur that we have observed in chronic experiments. When HFB in AD increased to the kindled level, 1 mM ZD7288 was injected with a rate of 1 μl/min 5 min before stimulating the ipsilateral side. Spectral analysis on each AD was performed with sampling frequency of 1 kHz by Power Lab (Chart, ADInstrument). Results: The power spectral density (PSD) ratios of the lower frequency band (LFB: 0-9 Hz), the middle frequency band (MFB: 9-12Hz) and HFB components against total PSD were calculated. During the acute kindling, PSD ratio of HFB component against total PSD changed from 15.4±9.5% (mean±SD) at the initial stage to 44.2±18.2 % (p<0.001) at the final stage. On the other hand PSD ratio of LFB component altered from 73.2±16.2 % to 36.8 ±17.3 %. ZD7288 suppressed kindling-induced ADs or retarded them, and decreased spontaneous seizure occurrence. In addition, even ADs after ZD7288 injection showed higher PSD ratio of LFB component . Conclusions: An enhancement of HFB component and decrement of LFB component in ADs also occurred in the acute kindling. Since ZD7288 suppressed seizure occurrence and enhancement of HFB component, it is suggested that Ih channels contribute to the generation of high frequency seizure discharge.