Devi P Uma, Manocha Anshu, Vohora Divya
Research Scientist (MACR) Ranbaxy Research Laboratories, Udyog Vihar Industrial Area, 20, Sector-18, IFFCO Road, Gurgaon 122015, Haryana, India.
Expert Opin Pharmacother. 2008 Dec;9(18):3169-77. doi: 10.1517/14656560802568230.
Neuronal hyperexcitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy. The high rate of oxidative metabolism, coupled with the low antioxidant defenses and the richness in polyunsaturated fatty acids, makes the brain highly vulnerable to free radical damage. The increased susceptibility of the brain to oxidative damage highlights the importance of understanding the role of oxidative stress in the pathophysiology of seizures.
The present review aims not only to address the link between mitochondrial dysfunction, oxidative stress and seizures, but also the modulation of the pro-oxidant/antioxidant balance following seizures and treatment with antioxidants and antiepileptic drugs.
A literature review revealed that there are articles that address the role of oxidative stress and mitochondrial dysfunction in neurological disorders, including those involving different seizure models where the modulation of the pro-oxidant/antioxidant balance by seizures per se and by antioxidant agents is discussed. However, the critical role of oxidative stress in all seizure models is not uniform. Therefore, there is a need for a review article that will address all these issues together.
RESULTS/CONCLUSIONS: The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of certain seizure types. The pro-oxidant/antioxidant balance is not only modulated by seizures per se, but also by antiepileptic drugs. The ability of antioxidants for reducing the seizure manifestations and the accompanying biochemical changes (i.e., markers of oxidative stress) further supports a role of free radicals in seizures and highlights a possible role of antioxidants as adjuncts to antiepileptic drugs for better seizure control.
神经元兴奋性过高和自由基的过度产生与包括癫痫在内的多种神经系统疾病的发病机制有关。大脑的氧化代谢率高，抗氧化防御能力低，且富含多不饱和脂肪酸，这使得大脑极易受到自由基损伤。大脑对氧化损伤易感性的增加凸显了了解氧化应激在癫痫病理生理学中作用的重要性。
本综述不仅旨在探讨线粒体功能障碍、氧化应激与癫痫之间的联系，还将探讨癫痫发作后以及使用抗氧化剂和抗癫痫药物治疗后促氧化剂/抗氧化剂平衡的调节情况。
文献综述表明，有文章探讨了氧化应激和线粒体功能障碍在神经系统疾病中的作用，包括那些涉及不同癫痫模型的文章，其中讨论了癫痫发作本身以及抗氧化剂对促氧化剂/抗氧化剂平衡的调节。然而，氧化应激在所有癫痫模型中的关键作用并不一致。因此，需要一篇综述文章来综合探讨所有这些问题。
结果/结论：实验和临床数据表明氧化应激在某些癫痫类型的病理生理学中可能发挥作用。促氧化剂/抗氧化剂平衡不仅受癫痫发作本身的调节，还受抗癫痫药物的调节。抗氧化剂降低癫痫发作表现及伴随生化变化（即氧化应激标志物）的能力进一步支持了自由基在癫痫中的作用，并凸显了抗氧化剂作为抗癫痫药物辅助剂以更好控制癫痫发作的可能作用。
