In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures
In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures
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DOI：
10.1038/nn1125
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发表时间：
2003-10-01
影响因子：
25
通讯作者：
Ben-Ari, Y
中科院分区：
文献类型：
--
作者：
Khalilov, I;Holmes, GL;Ben-Ari, Y
我们已经确定癫痫发作是否产生一个致痫灶的远端结构，使用在体外制备组成的三个独立的腔室，容纳两个完整的小脑和他们的连接连合。这使我们能够将惊厥剂应用于一个海马，允许将给定数量的癫痫发作传播到另一侧，并通过将河豚毒素（TTX）应用于连合室来可逆地阻断连接。癫痫发作从红藻氨酸治疗侧传播到幼稚侧，将后者转化为能够产生自发性和诱发性癫痫发作的独立致痫灶。诱导机制需要激活NMDA受体，致痫性转化与GABA能突触的长期改变有关，由于氯逆转电位E-Cl的变化，GABA能突触变得兴奋。这些数据表明，GABA的兴奋作用可能是致痫结构的基本性质。
We have determined whether seizures generate an epileptogenic focus in distal structures using an in vitro preparation composed of three independent chambers that accommodate two intact hippocampi and their connecting commissures. This enabled us to apply a convulsive agent to one hippocampus, allow the propagation of a given number of seizures to the other side and block the connections reversibly by applying tetrodotoxin (TTX) to the commissural chamber. The propagation of seizures from the kainate-treated side to the naive side transformed the latter into an independent epileptogenic focus that was capable of generating spontaneous and evoked seizures. The induction mechanism required activation of NMDA receptors and the epileptogenic transformation was associated with long-term alterations in GABAergic synapses, which became excitatory because of a shift in the chloride reversal potential, E-Cl. These data indicate that the excitatory actions of GABA may be a fundamental property of epileptogenic structures.