When and how do seizures kill neurons, and is cell death relevant to epileptogenesis?
When and how do seizures kill neurons, and is cell death relevant to epileptogenesis?
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DOI：
10.1007/978-94-017-8914-1_9
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发表时间：
2014
影响因子：
--
通讯作者：
Dudek FE
中科院分区：
文献类型：
--
作者：
Dingledine R;Varvel NH;Dudek FE
癫痫发作对神经元死亡的影响以及癫痫诱导的神经元死亡在获得性癫痫发生中的作用已经争论了几十年。孤立的短暂癫痫发作可能不会杀死神经元;然而，严重和重复性癫痫发作（即，癫痫持续状态）当然可以。由于癫痫持续状态既杀死神经元又导致慢性癫痫，因此神经元死亡被认为是获得性癫痫发生的一个组成部分。一些研究，特别是在未成熟的大脑中，已经表明神经元死亡不是获得性癫痫发生所必需的;然而，缺乏神经元死亡是困难的，如果不是不可能证明的话，最近的研究已经挑战了这一概念。细胞死亡的新机制，超越了传统的坏死和凋亡的概念，包括自噬，吞噬，坏死凋亡，和焦亡。关于癫痫发生中神经元死亡的传统观点是基于发育重演假说，即死亡神经元突触输入的丢失被认为是诱导轴突发芽和突触回路重组的关键信号。我们提出了第二个假说-神经元死亡途径假说，该假说指出，导致程序性神经变性的生化途径，而不是神经元死亡本身，是癫痫发生的原因。神经元死亡途径的重编程-如果是真的-被认为是源于坏死性凋亡或焦亡。提出的新假设可能会告知为什么神经元死亡似乎与癫痫发生密切相关，但可能并不总是如此。
The effect of seizures on neuronal death and the role of seizure-induced neuronal death in acquired epileptogenesis have been debated for decades. Isolated brief seizures probably do not kill neurons; however, severe and repetitive seizures (i.e., status epilepticus) certainly do. Because status epilepticus both kills neurons and also leads to chronic epilepsy, neuronal death has been proposed to be an integral part of acquired epileptogenesis. Several studies, particularly in the immature brain, have suggested that neuronal death is not necessary for acquired epileptogenesis; however, the lack of neuronal death is difficult if not impossible to prove, and more recent studies have challenged this concept. Novel mechanisms of cell death, beyond the traditional concepts of necrosis and apoptosis, include autophagy, phagoptosis, necroptosis, and pyroptosis. The traditional proposal for why neuronal death may be necessary for epileptogenesis is based on the recapitulation of development hypothesis, where a loss of synaptic input from the dying neurons is considered a critical signal to induce axonal sprouting and synaptic-circuit reorganization. We propose a second hypothesis – the neuronal death pathway hypothesis, which states that the biochemical pathways causing programmed neurodegeneration, rather than neuronal death per se, are responsible for or contribute to epileptogenesis. The reprogramming of neuronal death pathways – if true – is proposed to derive from necroptosis or pyroptosis. The proposed new hypothesis may inform on why neuronal death seems closely linked to epileptogenesis, but may not always be.