Dudek F Edward, Hellier Jennifer L, Williams Philip A, Ferraro Damien J, Staley Kevin J
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80523, USA.
Prog Brain Res. 2002;135:53-65. doi: 10.1016/S0079-6123(02)35007-6.
Chronic epilepsy, as a consequence of status epilepticus, has been studied in animal models in order to analyze the cellular mechanisms responsible for the subsequent occurrence of spontaneous seizures. Status epilepticus, induced by either kainic acid or pilocarpine or by prolonged electrical stimulation, causes a characteristic pattern of neuronal death in the hippocampus; which is followed--after an apparent latent period--by the development of chronic, recurrent, spontaneous seizures. The question most relevant to this conference is the degree to which the subsequent chronic seizures contribute further to epileptogenesis and brain damage. This article addresses the temporal and anatomical parameters that must be understood in order to address this question. (1) How does one evaluate experimentally whether the chronic epileptic seizures that follow status epilepticus contribute to epileptogenesis and lead to brain damage? To answer this question, we must first know the time course of the development of the chronic epileptic seizures, and whether the interval between subsequent individual chronic seizures is a relevant factor. (2) What anatomical parameters are most relevant to the progression of epilepsy? For instance, how does loss of inhibitory interneurons potentially influence seizure generation and the progressive development of epileptogenesis? Does axon sprouting and formation of new synaptic connections represent a form of seizure-induced brain damage? These specific issues bear directly on the general question of whether seizures damage the brain during the chronic epilepsy that follows status epilepticus.
慢性癫痫作为癫痫持续状态的后果，已在动物模型中进行研究，以分析导致随后自发性癫痫发作的细胞机制。由 kainic 酸或毛果芸香碱或通过长时间电刺激诱发的癫痫持续状态，会在海马体中引发一种特征性的神经元死亡模式；在明显的潜伏期之后，会出现慢性、复发性、自发性癫痫发作。与本次会议最相关的问题是，随后的慢性癫痫发作在多大程度上会进一步促进癫痫发生和脑损伤。本文探讨了为解决这个问题必须了解的时间和解剖学参数。（1）如何通过实验评估癫痫持续状态后出现的慢性癫痫发作是否会促进癫痫发生并导致脑损伤？为了回答这个问题，我们首先必须了解慢性癫痫发作的发展时间进程，以及随后个体慢性癫痫发作之间的间隔是否是一个相关因素。（2）哪些解剖学参数与癫痫的进展最相关？例如，抑制性中间神经元的丧失如何潜在地影响癫痫发作的产生和癫痫发生的渐进发展？轴突发芽和新突触连接的形成是否代表一种癫痫发作诱导的脑损伤形式？这些具体问题直接关系到癫痫发作在癫痫持续状态后的慢性癫痫过程中是否会损害大脑这个一般性问题。
