An electrophysiological study on the mechanism of seizure generation in rat brain slices : the effect of adenosine on epileptiformactivities.

大鼠脑切片癫痫发作机制的电生理学研究：腺苷对癫痫样活动的影响。

• 批准号: 04670847
• 负责人: KOJIMA Hisashi
• 金额: $ 1.34万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670847/
• 关键词: Epilepsy; Brain slices; Magnesium; Adenosine; Seizure; Interictal bursting; Hippocampus; Entorhinal cortex

Bathing rat brain slice containing hippocampus(HC) and entorhinal cortex(EC) in magnesium-free(0-Mg) medium elicits electrographic seizures. They are eventually replaced by interictal bursts(IIBs), which have been shown to arise in hippocampal area CA3 and suppress seizure generation in EC.We have reported that during this IIB phase, the exposure to hypoxia suppresses IIBs in CA3 and promotes seizure reappearance in EC.These data suggest that hypoxia may play an important role in the transition between IIBs and seizures. On the other hand, it has been reported that adenosine suppresses the neuronal activity during hypoxia. Given these findings, the present study examined the effect of adenosine and its antagonist theophylline on the epileptiform activities in order to investigate the mechanisms underlying the transition from IIBs to seizures in this model.Extracellular recordings were made in area CA3 and EC or HC/EC slices from Sprague-Dawley rats. In the 0-Mg medium, seizures appeared first but eventually they gave way to IIBs in both regions. After the seizures were completely replaced by IIBs, adenosine(50-100muM) was applied to the extracellularsolution. The IIBs in CA3 were suppressed in all the slices tested(n=33), while in EC the seizures reappeared in 28 slices(85%). In the theophylline experiments, hypoxia was introduced by switcihg the oxygenation gas from 95%O_2+5%CO_2 to 30%O_2+65%N_2+5%CO_2 during the IIB phase, then 100muM theophylline was added to the solutino(n=14). The EC-seizures reappeared in the hypoxic condition, however, theophylline blocked the effect and they were replaced by IIBs again.In conclusion, adenosine is one of the modulatory factors withch can promote the transition from IIBs to seizures in this O-Mg/hypoxia model.

无镁（0-Mg）介质诱发癫痫发作的大鼠海马（HC）和内嗅皮层（EC）脑片。我们报道了在发作间期（IIB）时相，缺氧抑制了海马CA 3区的IIB，并促进了EC的发作再现，提示缺氧可能在IIB和发作的转换中起重要作用。另一方面，有报道称腺苷抑制缺氧期间的神经元活动。鉴于这些发现，本研究探讨腺苷及其拮抗剂茶碱对癫痫样活动的影响，以探讨在这个模型中从IIB到癫痫发作的转变的机制。在0-Mg培养基中，癫痫发作首先出现，但最终在两个区域都让位于IIB。在癫痫发作完全被IIB所取代后，将腺苷（50- 100 μ M）施加到细胞外溶液中。CA 3的IIB在所有测试的切片中均被抑制（n=33），而EC中28个切片（85%）再次出现癫痫发作。在茶碱实验中，在IIB期将氧合气体从95%O_2+5%CO_2切换到30%O_2+65%N_2+5%CO_2，引入缺氧，然后向溶液中加入100 μ M茶碱（n=14）。缺氧条件下，EC-癫痫发作再次出现，但茶碱阻断了这种作用，IIB再次取代EC-癫痫发作。结论：在O-Mg/缺氧模型中，腺苷是促进IIB向癫痫发作转变的调节因子之一。