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--双侧海马点燃(BK)，并观察超极化依赖的钠/钙电流(IH)阻断剂氯化铯(CSCL)对BK致痫的影响。第一个实验结果如下：所有动物(n=17)在平均28次刺激后均出现5级惊厥。与单侧点燃动物(n=10)相比，双侧点燃过程显著增加点燃成功率(100%比59%；p&lt；0.01)，而显著减慢点燃进程(28d比19d；p&lt；0.02)。我们的结论是，BK过程代表了兴奋和抑制机制的增强，BK为研究点燃的发病机制和筛选抗惊厥药物提供了一个先进的动物模型。我们报道了一种持久的…在癫痫放电开始之前，更多的海马区中间神经元爆发放电，并且点燃期间锥体树突的异常活性(Kogure，Epelepsy Res.，1997)。最近的研究表明，Ih发生在海马锥体细胞的顶端树突中(Tsubokawa等人)。J.Physiol，1999)。为了验证我们关于Ih诱导癫痫放电的奇怪假设，我们在急性实验和BK程序中研究了CsCL对阵发性放电(PAD)的影响。在20例病例中，组织学确定了电极在海马CA1区放射层或腔隙分子中的位置。对照组(n=7)注射前PAD阈值为183±8μA，注射生理盐水后PAD阈值为190±8μA。而注射10 0 mM氯化铯后，PAD阈值显著升高(P<0.0 1)，达到316±9μA(n=7)，而注射前PAD阈值仍接近正常水平(16 7±7μA)。同样剂量的10 mM氯化铯(n=6)产生相似的效应：132±6μA对318±10μA)。另一方面，研究侧脑室注射CsCl2对兔海马区BK的慢性影响。一只动物表现出点燃过程的减慢，而另一只动物则表现出加速作用。结论：CSCL可以提高PAD阈值，并且IH在癫痫的产生中扮演着奇怪的角色，这支持了我们关于异常超极化导致异常兴奋的悖论假说。随后研究CSCL对BK的药理作用将有助于回答CSCL是否是一种新的抗癫痫药物的问题。较少

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