Henshall David C, Murphy Brona M
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Curr Opin Pharmacol. 2008 Feb;8(1):75-81. doi: 10.1016/j.coph.2007.07.005. Epub 2007 Sep 10.
Experimental and human data have shown that certain seizures cause damage to brain. Such neuronal loss may result in cognitive impairments and perhaps contribute to the development or phenotype of emergent epilepsy. Recent work using genetically modified mice, Tat protein transduction, and viral vectors has shown functional effects of manipulating Bcl-2 and Bcl-w, heat shock proteins, caspases, and their regulators and endonucleases on neuronal death in models of status epilepticus. Ancillary effects on seizure induction and excitability thresholds have emerged for several genes suggesting additional properties of therapeutic potential. Differing hippocampal expression of certain Bcl-2 family genes, elevated endoplasmic reticulum stress chaperones, and death receptor pathway modulation in epilepsy patients support clinical relevance of this focus. These findings may yield potentially valuable adjunctive neuroprotective or anti-epileptogenic strategies.
实验和人体数据表明，某些癫痫发作会对大脑造成损害。这种神经元损失可能导致认知障碍，并可能促成新发癫痫的发展或表型。最近利用基因改造小鼠、Tat蛋白转导和病毒载体开展的研究表明，在癫痫持续状态模型中，操控Bcl-2和Bcl-w、热休克蛋白、半胱天冬酶及其调节因子和核酸内切酶对神经元死亡具有功能性影响。若干基因对癫痫发作诱导和兴奋性阈值产生了辅助作用，提示其具有潜在治疗特性。癫痫患者体内某些Bcl-2家族基因在海马体中的表达不同、内质网应激伴侣蛋白水平升高以及死亡受体途径受到调节，这些都支持了这一研究重点的临床相关性。这些发现可能会产生潜在有价值的辅助性神经保护或抗癫痫发生策略。
