Cinnamon and traumatic brain injury

肉桂和创伤性脑损伤

• 批准号: 10553165
• 负责人: KALIPADA PAHAN
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553165
• 关键词: Animal Model; Anti-Inflammatory Agents; Area; Behavioral; Benzoates; Binding; Brain; Cause of Death; Child; Chronic; Cinnamon - dietary; Demyelinations; Exhibits; FDA approved; Failure; Flavoring; Food Preservatives; I Kappa B-Alpha; Inflammation; Ligand Binding Domain; Ligands; Link; Medicine; Microglia; Military Personnel; Nature; Nonketotic Hyperglycinemia; Oligodendroglia; Outcome; Patients; Peroxisome Proliferator-Activated Receptors; Persons; Pharmacotherapy; Recording of previous events; Research; Risk; Sodium; Spices; Sri Lanka; TBI Patients; Testing; Traumatic Brain Injury; Urea cycle disorders; axon injury; comorbidity; disability; glial activation; inhibitor; injury-related death; mouse model; neuroinflammation; neuroprotection; novel; oligodendrocyte progenitor; remyelination; stem cells

Traumatic brain jury (TBI) and associated co-morbidities are important contributors of disability among military personnel. Therefore, it is an urgent need to find an effective, a safe and an economical solution for this. Axonal injury is an important contributor to the behavioral deficits observed following TBI. It is believed that axonal injury during TBI is potentiated by neuroinflammation and demyelination and/or failure to remyelination. Cinnamon is a commonly used flavoring material and its metabolite sodium benzoate (NaB) is a widely-used food preservative and a FDA-approved drug for the treatment of urea cycle disorders and non-ketotic hyperglycinemia in children. Here, we will examine an exciting hypothesis that cinnamon metabolite NaB binds to the ligand-binding domain of peroxisome proliferator-activated receptor beta (PPARβ) (Specific aim I) to induce anti-inflammation in microglia and promote maturation of OPCs (Specific aim II), resulting in neuroprotection in a mouse model of TBI (Specific aim III). A positive outcome of this cutting-edge merit proposal will delineate NaB as a new nontoxic ligand of PPARβ and enhance the possibility of attenuating microglial activation, promoting remyelination and treating TBI patients with cinnamon and its metabolite NaB as primary or adjunct therapy.

创伤性脑陪审团（TBI）和相关的合并症是重要的因素 军事人员之间的残疾。因此，迫切需要找到一个有效的，一个 安全和经济解决方案。轴突损伤是造成的重要因素 该行为定义了在TBI之后观察到的。相信在 TBI是通过神经炎症和脱髓鞘和/或未能实现的 再髓。肉桂是一种常用的调味材料及其代谢物 苯甲酸钠（NAB）是保存的广泛食品，是FDA批准的药物 儿童的尿素周期疾病和非4tocotic高血糖的治疗。这里， 我们将研究一个令人兴奋的假设，即肉桂代谢物NAB与 过氧化物组增殖物激活受体β（PPARβ）的配体结合结构域（PPARβ） （特定目的I）诱导小胶质细胞中的抗炎并促进成熟 OPC（特定AIM II），导致TBI小鼠模型中的神经保护（特定 AIM III）。这项尖端优点提议的积极结果将把NAB描述为 PPARβ的新型无毒配体，并增强了减弱小胶质细胞的可能性 激活，促进再髓并治疗肉桂患者及其TBI患者 代谢物NAB作为主要或辅助疗法。