Effects of cesium chloride on the bilateral hippocampal kindling.

氯化铯对双侧海马点火的影响。

• 批准号: 11670969
• 负责人: KOGURE Shinichi
• 金额: $ 1.54万
• 依托单位: SOKA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670969/
• 关键词: afterdischarge threshold; epileptogenesis; h-current; hippocampus; interictal discharge; kindling; Na channel; paroxysmal discharge; 後発射; 錐体細胞・樹状突起; 塩化セシウム; 抗てんかん薬

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

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）模型，并观察氯化铯（CsCl）对BK模型的影响（超极化依赖性Na/Ca电流）对BK诱导的兔海马癫痫发生的影响。第一个实验的结果如下：所有动物（n=17）在平均28次刺激后均发生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的动物的百分比（100%对59% ; p<0.01），而其显著减慢了点燃进展（28天对19天; p<0.02）。我们的结论是，BK程序代表了兴奋和抑制机制的增强，BK为研究点燃的致病机制和筛选抗惊厥药物提供了先进的动物模型。 ...更多信息 在癫痫发作放电开始之前海马中间神经元的爆发放电，以及在点燃期间锥体树突的异常活性特性（Kogure，Epelepsy Res.，1997年）。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年）。为了验证Ih诱发癫痫发作的假说，我们在急性实验和BK程序中观察了CsCl对阵发性放电（PADs）的影响。对照组（n=7）注射生理盐水前PAD阈值为183±8μA，注射生理盐水后为190±8μA。相反，在注射100 mM CsCl（n=7）后，PAD阈值显著增加（p<0.01）至316±9μA的水平，而在注射前保持接近对照水平（167±7μA）。相同剂量的10 mM CsCl（n=6）诱导了相似的效应：132±6 μA vs. 318±10μA）。另一方面，观察了侧脑室注射CsCl对兔脑束BK（n=2）的慢性效应。一只动物表现出减速的点燃进程，而另一个没有acceleration.It的结论，CsCl可以增加PAD阈值，也Ih在癫痫发作的产生中起着奇怪的作用，这支持了我们的矛盾的假设，即异常超极化诱导异常兴奋。随后的调查，检查药理作用的氯化铯BK将有助于回答这个问题，氯化铯是否是一种新的AED（抗癫痫药物）或没有。少

项目成果

S.Kogure,M.Kitayama,M.Nojima, et al.: "Effects of cesium chloride on the electrically induced paroxysmal discharges."Epilepsia. 41-s.7. 13 (2000)

S.Kogure、M.Kitayama、M.Nojima 等人：“氯化铯对电致阵发性放电的影响”。癫痫。

M.Kitayama et al.: "Several characteristics of bilateralkindling of the rabbit hippocampi."Epilepsia. 40-s.2. 121 (1999)

M.Kitayama 等人：“兔子海马双侧点燃的几个特征。”癫痫。

S.Kogure,M.Kitayama,Y.Matsuda: "Simultaneous kindling of the bilateral hippocampi : An advanced model for epilepsy research."Epilepsia. 41. 929-932 (2000)

S.Kogure，M.Kitayama，Y.Matsuda：“双侧海马的同时点燃：癫痫研究的先进模型。”癫痫。

M.Kitayama,Y.Matsuda,Y.Kato and S.Kogure: "Several characteristics of bilateral kinding of the rabbit hippocampi."Epolepsia. vol.40,s-2. 121 (1999)

M.Kitayama，Y.Matsuda，Y.Kato 和 S.Kogure：“兔子海马双侧分类的几个特征。”Epolepsia。

S.Kogure et al.: "Simultaneous kindling of the bilateral hippocampi : An advanced model for epilepsy research."Epilepsia. 41. 929-932 (2000)

S.Kogure 等人：“双侧海马体的同时点燃：癫痫研究的高级模型。”癫痫。