Wang Wei, Wu Yanfen, Zhang Guoliang, Fang Haibo, Wang Hongchao, Zang Hongmin, Xie Tao, Wang Weiping
Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China; Department of Neurology, Handan First Hospital, Handan, Hebei 056002, PR China.
Department of Neurology, Handan First Hospital, Handan, Hebei 056002, PR China.
Brain Res. 2014 Jan 28;1544:54-61. doi: 10.1016/j.brainres.2013.12.004. Epub 2013 Dec 10.
Epilepsy remains a major medical problem for which there is no effective treatment. Oxidative damage plays an important role in epilepsy pathogenesis and may represent a target for treatment of epilepsy. Recent studies have suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative damage and accumulation of toxic metabolites. This study evaluated the role of Nrf2-ARE signal pathway in protecting the brain from seizure-mediated damage. Wistar rats and Nrf2-deficient or control mice were chronic kindled in the amygdala. Sulforaphane (SF) was used to activate Nrf2-ARE signal pathway. The progression of kindling, the cognitive impairment and oxidative stress parameters were assessed to determine the extent of seizure-mediated brain damage. Our results indicate that activation Nrf2-ARE signal pathway with SF in hippocampus suppressed the progression of amygdala kindling, and also ameliorated the cognitive impairment and oxidative stress induced by epileptic seizure. These observations suggest that Nrf2-ARE signal pathway may represent a strategic target for epilepsy therapies.
癫痫仍然是一个主要的医学问题，目前尚无有效的治疗方法。氧化损伤在癫痫发病机制中起重要作用，可能是癫痫治疗的一个靶点。最近的研究表明，核因子E2相关因子2（Nrf2）在氧化应激条件下与抗氧化反应元件（ARE）结合，诱导抗氧化和II期解毒酶，从而减少氧化损伤和有毒代谢产物的积累。本研究评估了Nrf2-ARE信号通路在保护大脑免受癫痫发作介导损伤中的作用。将Wistar大鼠和Nrf2缺陷或对照小鼠在杏仁核进行慢性点燃。使用萝卜硫素（SF）激活Nrf2-ARE信号通路。评估点燃的进展、认知障碍和氧化应激参数，以确定癫痫发作介导的脑损伤程度。我们的结果表明，用SF激活海马中的Nrf2-ARE信号通路可抑制杏仁核点燃的进展，并改善癫痫发作诱导的认知障碍和氧化应激。这些观察结果表明，Nrf2-ARE信号通路可能是癫痫治疗的一个战略靶点。
