UCL Queen Square Institute of Neurology, University College London, Queen Square, London, WC1N, UK; Faculty of Medicine, School of Pharmacy, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
UCL Queen Square Institute of Neurology, University College London, Queen Square, London, WC1N, UK; Department of Pharmacology, Medical University of Innsbruck, Peter Mayr Strasse 1A, 6020, Innsbruck, Austria.
Redox Biol. 2019 Sep;26:101278. doi: 10.1016/j.redox.2019.101278. Epub 2019 Jul 19.
Many epilepsies are acquired conditions following an insult to the brain such as a prolonged seizure, traumatic brain injury or stroke. The generation of reactive oxygen species (ROS) and induction of oxidative stress are common sequelae of such brain insults and have been shown to contribute to neuronal death and the development of epilepsy. Here, we show that combination therapy targeting the generation of ROS through NADPH oxidase inhibition and the endogenous antioxidant system through nuclear factor erythroid 2-related factor 2 (Nrf2) activation prevents excessive ROS accumulation, mitochondrial depolarisation and neuronal death during in vitro seizure-like activity. Moreover, this combination therapy prevented the development of spontaneous seizures in 40% of animals following status epilepticus (70% of animals were seizure free after 8 weeks) and modified the severity of epilepsy when given to chronic epileptic animals.
许多癫痫是在大脑受到损伤后产生的，例如长时间的癫痫发作、脑外伤或中风。活性氧（ROS）的产生和氧化应激的诱导是这些脑损伤的常见后果，已被证明可导致神经元死亡和癫痫的发生。在这里，我们发现，通过 NADPH 氧化酶抑制靶向 ROS 的生成以及通过核因子红细胞 2 相关因子 2（Nrf2）激活靶向内源性抗氧化系统的联合治疗可防止体外类似癫痫发作活动期间 ROS 过度积累、线粒体去极化和神经元死亡。此外，这种联合治疗在癫痫持续状态后可预防 40%的动物出现自发性癫痫发作（70%的动物在 8 周后无癫痫发作），并且在给予慢性癫痫动物时可改变癫痫的严重程度。
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