Redox Control of Seizure-Induced Neuroinflammation.

氧化还原控制癫痫引起的神经炎症。

• 批准号: 10205182
• 负责人: MANISHA N PATEL
• 金额: $ 34.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205182
• 关键词: Adverse effects; Aging; Antioxidants; Arachidonic Acids; Brain; Cells; Chronic; Chronic Disease; Cognition; Cysteine; Data; Disease; Epilepsy; Erythroid; Genetic Transcription; Glutathione; Glutathione Disulfide; Goals; Grant; Human; Impaired cognition; Impairment; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Laboratories; Lead; Ligase; Link; Lipid Peroxidation; Mediating; Mediator of activation protein; Methods; Modeling; Nuclear; Oxidation-Reduction; Oxidative Stress; Process; Production; Rattus; Reactive Oxygen Species; Reduced Glutathione; Role; Seizures; Series; Signal Pathway; Signal Transduction; Status Epilepticus; Sulforaphane; Testing; Therapeutic Intervention; Tissues; Up-Regulation; Work; acquired epilepsy; base; cell type; cognitive function; comorbidity; cytokine; improved; in vivo; neuroinflammation; neuronal excitability; novel; novel therapeutics; preservation; prevent; repaired; synthetic enzyme; targeted treatment; therapeutic target

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.

炎症和氧化应激是两个已知的同时发生在人体中的重要过程