Freeze-dried Fruit: Prevention and Rehabilitation Strategies in TBI

描述(由申请人提供)： 创伤性脑损伤在美国人群和美国服役人员中都是一个重要的问题。与文职人员相比，在战区服役的已部署服务人员尤其面临持续TBI的风险。由于不同程度的冲击伤，可能会导致多处创伤，进一步使颅脑损伤的紧急治疗复杂化。到目前为止，还没有临床治疗方法被证明对治疗原发性脑外伤有效。因此，按照医学研究所最近的一份报告所建议的那样，开发减少炎症的支持性疗法将有望改善症状和/或减缓疾病进展。由于浆果含有高水平的抗氧化类黄酮，特别是花青素，而且似乎在外周和中枢神经系统组织中具有有益的免疫调节和抗炎特性，因此它们可能被证明对预防和/或治疗脑损伤有益。在氧化应激和炎症(电离辐射)的啮齿动物模型中，在饮食中添加浆果可以减少对对照水平的损害。此外，我们和其他人已经证明，适度添加浆果的饮食补充剂能够抑制和改善神经炎症和神经退化过程所导致的症状。我们推测，饮食补充全冷冻干燥浆果将有效预防和治疗创伤性脑损伤的神经炎性成分。因此，我们将通过检查以下特定目标来检验这一假设：目标1：测试浆果粉末对临床、组织学和炎症体征的影响。 在损伤发生前给予浆果的脑损伤大鼠模型。目的：测试浆果粉对大鼠模型的临床、组织学和炎症体征的影响。 在症状演变后给予浆果时，脑损伤的发生率。总而言之，浆果的抗氧化和抗炎特性提供了一个理想的策略，因为它们易于口服，毒性低，并且可以与其他药物联合使用。开发一种低成本、易耐受但没有现有治疗方法副作用的口服支持性治疗方法，将极大地改善对脑外伤患者的护理。 公共卫生相关性： 颅脑损伤可能占到所有战斗伤害的三分之一。虽然许多士兵似乎在几个月内就能从轻微的脑外伤中恢复过来，但10%到15%的人报告说，数年来一直存在认知困难。最初和随后的损害被认为是由氧化应激、代谢紊乱和炎症引起的。因此，减少炎症的药物有望降低损伤严重程度和长期残疾。浆果含有高水平的抗氧化剂类黄酮，具有有益的免疫调节和抗炎特性，并可能被证明对预防和/或治疗脑损伤有益。它们易于口服，毒性低，并可与其他药物联合使用。开发一种成本低、口服给药、易于耐受、副作用小的辅助疗法，将极大地改善暴露于脑外伤或患有脑外伤的患者的护理。

DESCRIPTION (provided by applicant): Traumatic Brain Injury (TBI) is a significant issue both in the US population and in US service personnel. Deployed service personnel serving in combat zones are especially at risk for sustaining a TBI when compared to their civilian peers. Poly-trauma may result due to varying levels of blast injury, further complicating immediate treatment for TBI. Thus far, no clinical treatments have proven effective for the treatment of primary TBI. Development of supportive therapies that decrease inflammation, as recommended in a recent report from the Institute of Medicine, would therefore be expected to improve symptoms and/or slow disease progression. Since berries contain high levels of the antioxidant flavonoids, particularly anthocyanins, and seem to possess beneficial immune modulatory and anti-inflammatory properties in the peripheral and central nervous system tissues, they may prove beneficial in prevention and/or treatment of TBI. In rodent models of oxidative stress and inflammation (ionizing radiation), addition of berries to the diet reduced damage from to control levels. Additionally, we and others have show that dietary supplementation with berries at a modest level is capable of both suppressing and ameliorating symptoms that are a result of neuroinflammatory and neurodegenerative processes. We hypothesize that dietary supplementation with whole- freeze dried berries will be efficacious in preventing and treating neuroinflammatory components of TBI. Therefore, we will test this hypothesis by examining the following specific aims: Objective 1: To test the effect of berry powders on clinical, histological, and inflammatory signs present in a rat model of TBI when berries are administered before the onset of injury. Objective 2: To test the effect of berry powder on clinical, histological, and inflammatory signs present in a rat model of TBI when berries are administered after the evolution of symptoms. In summary, the anti-oxidant and anti-inflammatory properties of berries provide an ideal strategy as they are easily administered orally, have low toxicity profiles and they can be combined with other medications. Development of an orally delivered supportive therapeutic that is low cost and easily tolerated but without the side effects of current treatments would greatly improve the care of patients suffering from TBI. PUBLIC HEALTH RELEVANCE: TBI may account for up to 1/3 of all combat injuries. Although many soldiers seem to recover from mild TBI within months, 10 to 15% report ongoing difficulty in cognition for years. Initial an subsequent damage are thought to be caused by oxidative stress, metabolic disturbances and inflammation. Agents that reduce inflammation are therefore expected to decrease injury severity and long-term disability. Berries contain high levels of the antioxidant flavonoids and have beneficial immune modulatory and anti-inflammatory properties and may prove beneficial in prevention and/or treatment of TBI. They are easily orally administered, have low toxicity profiles and can be combined with other medications. Development of a low cost, orally delivered, adjuvant therapy that is easily tolerated, and has a low side effect profile, would greatly improve the care of patients exposed to or suffering from TBI.