Effects of cesium chloride on the bilateral hippocampal kindling.

本实验旨在建立一种新的癫痫研究动物模型——海马双侧点燃（BK）模型，并研究氯化铯（CsCl）作为超极化依赖钠钙电流（Ih）阻滞剂对兔海马双侧点燃诱导的癫痫发生的影响。第一次实验的结果如下：所有动物（n=17）在平均28次刺激后出现5期惊厥。与单侧点燃动物（n=10）相比，双侧点燃程序显著增加了成功点燃动物的百分比（100% vs. 59%; p<0.01），而显著减缓了点燃进程（28天vs. 19天；p<0.02）。我们得出结论，BK过程代表了兴奋和抑制机制的增强，并且BK为研究引燃的致病机制和筛选抗惊厥药提供了一个先进的动物模型。我们已经报道了在癫痫发作开始之前海马中间神经元有一个持久的…更多的突发放电，以及在点燃期间锥体树突的异常活跃特性（Kogure, epilepsy Res., 1997）。最近的研究表明，Ih发生在海马锥体细胞的顶端树突（Tsubokawa等）。J.Physiol。, 1999)。为了验证我们关于Ih诱导癫痫发作放电的假设，我们在急性实验和BK程序中检查了CsCl对阵发性放电（PADs）的影响。在20例中，电极的位置在组织学上被确定在海马CA1的辐射层或空隙分子中。对照组（n=7）注射生理盐水前PAD阈值为183±8μA，注射生理盐水后PAD阈值为190±8μA。相比之下，注射100 mM CsCl后（n=7）的PAD阈值显著（p<0.01）升高至316±9μA，而注射前的PAD阈值接近对照组（167±7μ a）。相同剂量的CsCl （n=6）对小鼠的影响相似，分别为132±6 μA和318±10μA。另一方面，研究了侧脑室注射CsCl对兔海马BK的慢性影响（n=2）。一只动物表现出点火过程的减速，而另一只则表现出加速。结果表明，CsCl可以增加PAD阈值，并且Ih在癫痫发作中起着奇怪的作用，这支持了我们的反常超极化引起异常兴奋的矛盾假设。随后的研究将检验CsCl对BK的药理作用，这将有助于回答CsCl是否是一种新型抗癫痫药物的问题。少

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 … More 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