PYCNOGENOL AND TRAUMATIC 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的损失，使许多家庭在经济上陷入瘫痪。脑外伤涉及至少两个独立的损伤级联反应，导致神经元和认知功能障碍。继发性损伤级联可能适用于药物干预，但其机制复杂，需要多方面的研究。氧化应激、线粒体功能丧失和神经炎症似乎起着主要作用。天然产生的黄酮类化合物不仅具有巨大的自由基清除能力，而且还具有调节细胞稳态的能力，从而减少炎症和细胞毒性。提出的研究将调查碧萝芷酚(r) (PYC)，生物类黄酮的组合，可以显著减少脑外伤后的继发性损伤级联的想法。这是一种非常新颖的TBI治疗方法，因为它利用了从树皮中提取的一个非常密切相关的生物活性多酚家族。第一系列研究将探索PYC的最佳剂量，以最大限度地减少实验性TBI后啮齿动物的氧化应激和神经炎症。第二组研究将探讨PYC对实验性脑损伤后海马线粒体生物能量学和细胞存活的保护作用。这些研究的成功完成将为在更多实验性TBI研究中使用PYC铺平道路，并有助于开发合理的治疗方法，从而获得更有利的结果。

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.