Khalilov Ilgam, Holmes Gregory L, Ben-Ari Yehezkel
Institut de Neurobiologie de la Mediterranee (INMED)-INSERM U29, 163 Route de Luminy, Marseilles 13273, France.
Nat Neurosci. 2003 Oct;6(10):1079-85. doi: 10.1038/nn1125. Epub 2003 Sep 21.
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.
我们使用一种由三个独立腔室组成的体外制备方法，来确定癫痫发作是否会在远端结构中产生致痫灶，该制备方法可容纳两个完整的海马体及其连接连合。这使我们能够向一个海马体施加惊厥剂，让一定数量的癫痫发作传播到另一侧，并通过向连合腔室施加河豚毒素（TTX）来可逆地阻断连接。癫痫发作从经海藻酸处理的一侧传播到未处理的一侧，使后者转变为一个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NMDA受体的激活，并且致痫转化与GABA能突触的长期改变有关，由于氯离子反转电位E(Cl)的改变，GABA能突触变得具有兴奋性。这些数据表明，GABA的兴奋作用可能是致痫结构的一个基本特性。
