| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
The present experiments were disigned to establish a new animal model for epilepsy research which was named bilateral kindling (BK) of the hippocampi, and to reveal effects of cesium chloride (CsCl) which is a blocker to Ih (hyperpolarization-dependent Na/Ca current) on the epileptogenesis induced by BK of the rabbit hippocampi.
The results of the first experiment were as follows : All animals (n=17) developed stage 5 convulsions after a mean of 28 stimulations. Compared with unilateral kindled animals (n=10), the bilateral kindling procedure significantly increased the percentage of animals that successfully kindled (100% vs. 59% ; p<0.01), whereas it significantly decelerated the kindling progression (28 days vs. 19 days ; p<0.02). We conclude that the BK procedure represents potentiation of both excitatory and inhibitory mechanisms, and the BK provides an advanced animal model to study the pathogenic mechanisms of kindling and to screen anticonvulsants.
We have reported a long-lasting
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burst discharge of the hippocampal interneuron prior to the initiation of the seizure discharge, and also an abnormal active property of the pyramidal dendrite during kindling (Kogure, Epelepsy Res., 1997). Recent studies demonstrated that the Ih occurred in the apical dendrites of the hippocampal pyramidal cells (Tsubokawa et al. J.Physiol., 1999). To test our curious hypothesis that Ih induces the seizure discharge, effects of CsCl on the paroxysmal discharges (PADs) were examined in the acute experiment as well as in the BK procedure.
In twenty cases, the electrode locations were histologically identified in the stratum radiatum or lacunosum-moleculare of the hippocampus CA1. The threshold for PAD in the conrol group (n=7) was 183±8μA before, and 190±8μA after saline injection. In contrast, the PAD threshold significantly (p<0.01) increased to a level of 316±9μA after injecting 100 mM CsCl (n=7), while remaining nearly the control level (167±7μA) before the injection. The same dose of 10 mM CsCl (n=6) induced a similar effect : 132±6 μA vs. 318±10μA). On the other hand, the chronic effects of CsCl injection into the lateral ventricle were studied during BK of the rabbit hippocampi (n=2). One animal showed a decelaration of the kindling progression, whereas the other did an acceleration.
It is concluded that CsCl can increase the PAD threshold and also Ih plays a curious role in the seizure generation, which supports our paradoxical hypothesis that an anomalous hyperpolarization induces an abnormal excitation. A subsequent investigation that examines pharmacological effects of CsCl on BK will help answer the question whether CsCl is a novel AED (anti-epileptic drug) or not. Less
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