Holopainen Irma E
Department of Pharmacology, Drug Development and Therapeutics, and Medicity Research Laboratory, Institute of Biomedicine, University of Turku, Tykistökatu 6A, FIN-20014 Turku, Finland.
Neurochem Int. 2008 May;52(6):935-47. doi: 10.1016/j.neuint.2007.10.021. Epub 2007 Nov 17.
Epilepsy is a common neurological disorder that occurs more frequently in children than in adults. The extent that prolonged seizure activity, i.e. status epilepticus (SE), and repeated, brief seizures affect neuronal structure and function in both the immature and mature brain has been the subject of increasing clinical and experimental research. Earlier studies suggest that seizure-induced effects in the immature brain compared with the adult brain are different. This is manifested as differences in neuronal vulnerability, cellular and synaptic reorganization and regenerative processes. The focus of this review is first to give a short overview of currently used experimental models of epilepsy in immature rats, and then discuss more thoroughly seizure-induced acute and sub-acute cellular and molecular alterations, highlight the contribution of inflammatory-like reactions and intracellular cytoskeleton to the insult, and reveal changes in the structure and function of inhibitory GABA(A) and excitatory glutamate receptors. The role of seizure-activated reparative, plastic processes, synaptic remodelling, neurogenesis as well as the long-term consequences of seizures are briefly outlined. The main emphasis is put on studies carried out in experimental animals, and the focus of interest is the hippocampus, the brain area of great vulnerability in epilepsy. In vitro studies are discussed only to limited extent. Collectively, recent studies suggest that the deleterious effects of seizures may not solely be a consequence of neuronal damage and loss per se, but could be due to the fact that seizures interfere with the highly regulated developmental processes in the immature brain.
癫痫是一种常见的神经系统疾病，在儿童中比在成人中更频繁地发生。长时间的癫痫发作活动，即癫痫持续状态（SE），以及反复的短暂发作对未成熟和成熟大脑中神经元结构和功能的影响程度，一直是越来越多临床和实验研究的主题。早期研究表明，与成人大脑相比，未成熟大脑中癫痫发作诱导的效应有所不同。这表现为神经元易损性、细胞和突触重组以及再生过程的差异。本综述的重点首先是简要概述目前在未成熟大鼠中使用的癫痫实验模型，然后更深入地讨论癫痫发作诱导的急性和亚急性细胞及分子改变，强调炎症样反应和细胞内细胞骨架对损伤的作用，并揭示抑制性GABA(A)受体和兴奋性谷氨酸受体的结构和功能变化。简要概述了癫痫发作激活的修复、可塑性过程、突触重塑、神经发生以及癫痫发作的长期后果。主要重点放在实验动物的研究上，感兴趣的焦点是海马体，它是癫痫中极易受损的脑区。体外研究仅在有限程度上进行了讨论。总体而言，最近的研究表明，癫痫发作的有害影响可能不仅仅是神经元损伤和损失本身的结果，还可能是因为癫痫发作干扰了未成熟大脑中高度调节的发育过程。
