Jimenez-Mateos Eva M, Henshall David C
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
Int J Physiol Pathophysiol Pharmacol. 2009 Nov 2;1(2):180-191.
One or more brief seizures can serve to activate endogenous protective programmes which render brain regions temporarily less susceptible to damage following an otherwise harmful episode of status epilepticus (a prolonged seizure). Epileptic tolerance has been demonstrated using a variety of seizure preconditioning paradigms, including electroconvulsive shocks and low doses of excitotoxins such as kainic acid. The cell and molecular mechanisms underlying the protection are not fully understood but proposed mediators include the transcription factor NfκB, altered ion channel expression, upregulation of growth factors and other protective genes, and suppression of pro-apoptotic Bcl-2 family proteins. Application of microarrays to profile the transcriptome of seizure-preconditioning and tolerance has provided further insights, including roles for chromatin remodeling and evidence that preconditioning generates an anti-excitotoxicity phenotype by reprogramming the transcriptional response to status epilepticus. This review summarizes the various animal models of epileptic tolerance, reviews the key effector(s) and the utility of this experimental paradigm for identifying novel targets for neuroprotection and anti-epileptogenesis.
一次或多次短暂发作可激活内源性保护程序，使脑区在随后发生的有害癫痫持续状态（长时间发作）期间暂时降低对损伤的易感性。使用多种癫痫预处理范式已证实了癫痫耐受性，包括电惊厥休克和低剂量兴奋性毒素（如 kainic 酸）。保护作用背后的细胞和分子机制尚未完全了解，但推测的介质包括转录因子 NfκB、离子通道表达改变、生长因子和其他保护基因的上调，以及促凋亡 Bcl-2 家族蛋白的抑制。应用微阵列分析癫痫预处理和耐受性的转录组提供了进一步的见解，包括染色质重塑的作用以及预处理通过重新编程对癫痫持续状态的转录反应产生抗兴奋性毒性表型的证据。本综述总结了癫痫耐受性的各种动物模型，回顾了关键效应因子以及该实验范式在识别神经保护和抗癫痫发生新靶点方面的实用性。
