PYCNOGENOL AND TRAUMATIC BRAIN INJURY

碧萝芷与脑外伤

• 批准号: 7942792
• 负责人: STEPHEN W SCHEFF
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942792
• 关键词: Age; Animal Model; Animals; Antioxidants; Apoptosis; Bioenergetics; Bioflavonoid; Brain; Brain Injuries; Caring; Cause of Death; Cell Death; Cell Survival; Cells; Cessation of life; Complex; Development; Dose; Early treatment; Elements; Experimental Models; Family; Flavonoids; Free Radical Scavengers; Free Radical Scavenging; Hippocampus (Brain); Homeostasis; Impaired cognition; Income; Individual; Inflammation; Injury; Intervention; Lead; Legal patent; Length; Longitudinal Studies; Membrane; Methods; Mitochondria; Monitor; Neurocognition; Neuronal Dysfunction; Neurons; Outcome; Outcome Measure; Oxidants; Oxidative Stress; Pathogenesis; Pharmaceutical Preparations; Pinus maritima; Play; Population; Property; Proteins; Pycnogenol; Reactive Nitrogen Species; Reactive Oxygen Species; Recovery; Rehabilitation therapy; Research; Rodent; Role; Series; Staining method; Stains; Stress; Synapses; Testing; Therapeutic; Time; Toxic effect; Trauma; Traumatic Brain Injury; Tree Bark; United States; Work; clinical care; cohort; cytokine; disability; fluoro jade; global health; long term hospitalization; macrophage; neurobehavioral; neuroinflammation; novel strategies; polyphenol; public health relevance; research study; response

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a global health problem that is financially crippling for many families because of both specialized care and lost financial income. TBI involves at least two separate injury cascades that lead to neuronal and cognitive dysfunction. The secondary injury cascade may be amenable to pharmacologic intervention but the mechanisms are complicated requiring a multi-faceted approach. Oxidative stress, loss of mitochondrial function, and neuroinflammation appear to play major roles. Naturally occurring flavonoids are unique in possessing not only tremendous free radical scavenging properties but also the ability to modulate cellular homeostasis leading to a reduction in inflammation and cell toxicity. The proposed studies will investigate the idea that Pycnogenol(r) (PYC), a combination of bioflavonoids, can significantly reduce the secondary injury cascade following TBI. This is an extremely novel approach to TBI therapy since it utilizes a family of very closely related biologically active polyphenols derived from tree bark. The first series of studies will explore the best possible dosing of PYC to maximally reduce oxidative stress and neuroinflammation following experimental TBI in rodents. The second set of studies will explore the protective qualities of PYC on mitochondrial bioenergetics and cell survival in the hippocampus following experimental TBI. Successful completion of the studies will pave the way for using PYC in more involved experimental TBI studies and contribute to the development of a rational therapy leading to a more favorable outcome. PUBLIC HEALTH RELEVANCE: The proposed studies investigate a specialized compound, called a bioflavonoid, to determine if it can help protect cells in the brain following injury. Using a well characterized animal model of traumatic brain injury, subjects are treated with the compound, Pycnogenol(r), and tested for a variety of outcome measures. Bioflavonoids are known to manifest multiple different helpful properties such as reducing oxidative stress. If the studies work, then more complex and longer term studies can be proposed, hopefully leading to a more rational therapy for brain injury.

描述（由申请人提供）：创伤性脑损伤（TBI）是一个全球性的健康问题，由于专业护理和经济收入损失，许多家庭在经济上陷入困境。TBI涉及至少两个独立的损伤级联，导致神经元和认知功能障碍。继发性损伤级联反应可能适合于药物干预，但其机制是复杂的，需要多方面的方法。氧化应激、线粒体功能丧失和神经炎症似乎起主要作用。天然存在的黄酮类化合物是独特的，不仅具有巨大的自由基清除性能，而且还具有调节细胞内稳态的能力，从而减少炎症和细胞毒性。拟议中的研究将调查碧萝芷（r）（PYC），一种双氯芬酸的组合，可以显着减少TBI后的继发性损伤级联反应的想法。这是一种非常新颖的TBI治疗方法，因为它利用了一个非常密切相关的生物活性多酚家族，这些多酚来源于树皮。第一系列研究将探索PYC的最佳剂量，以最大限度地减少啮齿动物实验性TBI后的氧化应激和神经炎症。第二组研究将探索PYC对实验性TBI后海马中线粒体生物能量学和细胞存活的保护质量。这些研究的成功完成将为PYC在更多涉及的实验性TBI研究中的应用铺平道路，并有助于开发一种合理的治疗方法，从而获得更有利的结果。 公共卫生关系：拟议中的研究调查了一种名为生物素的特殊化合物，以确定它是否可以帮助保护受伤后的大脑细胞。使用创伤性脑损伤的良好表征的动物模型，受试者用化合物碧萝芷治疗，并测试各种结果测量。众所周知，双歧杆菌具有多种不同的有益特性，如减少氧化应激。如果这些研究有效，那么可以提出更复杂和更长期的研究，希望能为脑损伤带来更合理的治疗方法。