Puttachary Sreekanth, Sharma Shaunik, Stark Sara, Thippeswamy Thimmasettappa
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Biomed Res Int. 2015;2015:745613. doi: 10.1155/2015/745613. Epub 2015 Jan 20.
An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.
脑部受到损伤（如首次癫痫发作）会引发兴奋性毒性、神经炎症以及活性氧/氮物种（ROS/RNS）的产生。癫痫持续状态（SE）期间产生的ROS和RNS使线粒体的天然抗氧化防御机制不堪重负。这会导致线粒体功能障碍以及线粒体DNA损伤。进而影响参与电子传递链的各种酶复合物的合成。癫痫发生过程中产生的后果包括脂质过氧化、反应性胶质增生、海马体神经退行性变、神经网络重组以及过度同步化。这些因素使大脑易发生自发性复发性癫痫（SRS），最终发展为颞叶癫痫（TLE）。本综述讨论了其中的一些问题。尽管抗癫痫药物（AEDs）有助于控制/抑制癫痫发作，但在动物模型和人类患者中，长期使用这些药物已被证明会增加ROS/RNS。在已确诊的TLE中，ROS/RNS被证明是有害的，因为它们会增加对SRS的易感性。此外，在本文中，我们简要回顾了来自动物模型和人类TLE患者的数据，这些数据涉及抗癫痫药物的不良反应以及抗氧化剂作为辅助治疗可能产生的改善作用。
