Patel Manisha
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Free Radic Biol Med. 2004 Dec 15;37(12):1951-62. doi: 10.1016/j.freeradbiomed.2004.08.021.
Mitochondrial dysfunction has been implicated as a contributing factor in diverse acute and chronic neurological disorders. However, its role in the epilepsies has only recently emerged. Animal studies show that epileptic seizures result in free radical production and oxidative damage to cellular proteins, lipids, and DNA. Mitochondria contribute to the majority of seizure-induced free radical production. Seizure-induced mitochondrial superoxide production, consequent inactivation of susceptible iron-sulfur enzymes, e.g., aconitase, and resultant iron-mediated toxicity may mediate seizure-induced neuronal death. Epileptic seizures are a common feature of mitochondrial dysfunction associated with mitochondrial encephalopathies. Recent work suggests that chronic mitochondrial oxidative stress and resultant dysfunction can render the brain more susceptible to epileptic seizures. This review focuses on the emerging role of oxidative stress and mitochondrial dysfunction both as a consequence and as a cause of epileptic seizures.
线粒体功能障碍被认为是多种急慢性神经疾病的一个促成因素。然而，其在癫痫中的作用直到最近才显现出来。动物研究表明，癫痫发作会导致自由基产生以及对细胞蛋白质、脂质和DNA的氧化损伤。线粒体是癫痫发作诱导产生的自由基的主要来源。癫痫发作诱导的线粒体超氧化物生成、随后易感铁硫酶（如乌头酸酶）的失活以及由此产生的铁介导毒性可能介导癫痫发作诱导的神经元死亡。癫痫发作是与线粒体脑病相关的线粒体功能障碍的一个常见特征。最近的研究表明，慢性线粒体氧化应激及其导致的功能障碍会使大脑更容易发生癫痫发作。本综述重点关注氧化应激和线粒体功能障碍作为癫痫发作的后果和原因所起的新作用。
