Redox Control of Seizure-Induced Neuroinflammation.

炎症和氧化应激是已知的两个同时发生在 癫痫。神经炎是公认的获得性癫痫的媒介，并且是一种高度 调查对象为治疗干预对象。谷胱甘肽耗竭发生在侮辱 引起癫痫及其补充可以改变癫痫发作和认知障碍。最近的工作在 我们的实验室已经证明，谷胱甘肽的升高可以抑制神经炎症。从长远来看 这项建议的目标是通过提高获得性癫痫模型中的脑谷胱甘肽水平 新机制，即直接翻译后激活其限速合成酶- 谷氨酰半胱氨酸连接酶。这项提议的目标是检验这样一个假设，即增加从头开始 谷胱甘肽的合成可减少神经炎症、癫痫发作和/或认知功能障碍。 瞄准。1将测试选定的化合物提高谷胱甘肽、抑制神经炎症的能力 以及体外神经元的兴奋性。目标2将确定化合物是否能够提升 谷胱甘肽可抑制癫痫发作、癫痫和/或认知功能障碍。这些研究可以确定一种 减轻获得性癫痫神经炎症的新机制及基于氧化还原的建议 治疗癫痫及相关合并症的化合物。

Inflammation and oxidative stress are two important processes known to occur concurrently in epilepsy. Neuroinflammation is a well-recognized mediator of acquired epilepsy and a highly investigated target for therapeutic intervention. Glutathione depletion occurs following insults that cause epilepsy and its repletion can modify seizures and cognitive impairment. Recent work in our laboratory has shown that elevation of glutathione can inhibit neuroflammation. The long term goal of this proposal is to elevate brain glutathione levels in models of acquired epilepsy by a novel mechanism i.e. direct posttranslational activation of its rate-limiting synthetic enzyme, - glutamyl cysteine ligase. The goal of this proposal is to test the hypothesis that increased de novo synthesis of glutathione decreases neuroinflammation, seizures and/or cognitive dysfunction. Aim. 1 will test select compounds for their ability to increase glutathione, inhibit neuroinflammation and neuronal excitability in vitro. Aim 2 will determine if compounds capable of elevating glutathione inhibit seizures, epilepsy and/or cognitive dysfunction. These studies can identify a novel mechanism of reducing neuroinflammation in acquired epilepsy and suggest redox-based compounds for the treatment of epilepsy and associated comorbidities.