Valenzuela V, Benardo L S
Department of Neurology, State University of New York Health Science Center, Brooklyn 11203, USA.
Epilepsy Res. 1995 Jul;21(3):195-204. doi: 10.1016/0920-1211(95)00024-5.
An in vitro model of persistent epileptiform activity was developed to study the mechanisms involved in epileptogenesis. Extracellular recordings were obtained from rat neocortical slices exposed to magnesium-free solution for 2 h. During exposure to magnesium-free solution spontaneous epileptiform activity consisting of interictal bursting and ictal-like discharges were observed. Interestingly, this activity persisted for hours after the slices were returned to magnesium-containing control solution. The N-methyl-D-aspartate (NMDA) receptor antagonist CPP prevented the development of the epileptiform activity, while the non-NMDA receptor antagonist CNQX abolished the epileptiform discharge that persisted after slices were returned to control solution. These findings suggest there are two distinct phases in the development of epileptic activity in this model, namely, induction (mediated by NMDA receptor activity) and maintenance (supported largely by non-NMDA receptor activity). The similarities and possible parallels between the mechanisms underlying this epileptogenesis and other forms of use-dependent modification of synaptic excitation, such as long-term potentiation, are discussed. This in vitro model of neocortical epileptogenesis may provide insights into the events underlying the development of clinical partial epilepsy.
为了研究癫痫发生的机制，建立了一种持续性癫痫样活动的体外模型。从暴露于无镁溶液2小时的大鼠新皮质切片中获得细胞外记录。在暴露于无镁溶液期间，观察到由发作间期爆发和发作样放电组成的自发性癫痫样活动。有趣的是，在切片回到含镁对照溶液后，这种活动持续了数小时。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂CPP可阻止癫痫样活动的发展，而非NMDA受体拮抗剂CNQX则消除了切片回到对照溶液后持续存在的癫痫样放电。这些发现表明，在该模型中癫痫活动的发展有两个不同阶段，即诱导（由NMDA受体活性介导）和维持（主要由非NMDA受体活性支持）。讨论了这种癫痫发生机制与其他形式的突触兴奋的使用依赖性修饰（如长时程增强）之间的相似性和可能的平行关系。这种新皮质癫痫发生的体外模型可能为临床部分性癫痫发展背后的事件提供见解。
