Cinnamon and traumatic brain injury

肉桂和创伤性脑损伤

• 批准号: 10438526
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438526
• 关键词: Animal Model; Anti-Inflammatory Agents; Area; Attenuated; 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; 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) 和相关合并症是导致脑损伤的重要因素 军事人员中的残疾。因此，迫切需要寻找一种有效的、 安全且经济的解决方案。轴突损伤是导致轴突损伤的重要原因 TBI 后观察到的行为缺陷。据认为，轴突损伤 神经炎症和脱髓鞘和/或未能预防 TBI 会加剧 髓鞘再生。肉桂是一种常用的调味物质及其代谢产物 苯甲酸钠 (NaB) 是一种广泛使用的食品防腐剂，也是 FDA 批准的药物 治疗儿童尿素循环障碍和非酮症高血糖症。这里， 我们将研究一个令人兴奋的假设，即肉桂代谢物 NaB 与 过氧化物酶体增殖物激活受体β (PPARβ) 的配体结合域 （具体目标一）诱导小胶质细胞抗炎并促进其成熟 OPC（特定目标 II），对 TBI 小鼠模型产生神经保护作用（特定目标 II） 目标三）。这项尖端优点提案的积极成果将把 NaB 描绘成一个 PPARβ的新无毒配体并增强减弱小胶质细胞的可能性 肉桂及其衍生物激活、促进髓鞘再生和治疗 TBI 患者 代谢物 NaB 作为主要或辅助治疗。