Freeze-dried Fruit: Prevention and Rehabilitation Strategies in TBI

冻干水果：TBI 的预防和康复策略

• 批准号: 8278776
• 负责人: SUSAN O MCGUIRE
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-11-01 至 2014-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278776
• 关键词: Accounting; Adjuvant; Adjuvant Therapy; Adverse effects; Aging; Animals; Anthocyanins; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Athletic Injuries; Behavioral; Berry; Blast Injuries; Blueberries; Clinical; Clinical Treatment; Cognition; Data; Development; Diet; Dietary Supplementation; Disease Progression; Dose; Elderly; Event; Evolution; Family; Flavonoids; Freeze Drying; Fruit; Hour; Human; Human Resources; Immune; Immune Cell Activation; Immunohistochemistry; Inflammation; Inflammatory; Injury; Institute of Medicine (U.S.); Ionizing radiation; Memory; Metabolic; Modeling; Myocardial Infarction; Nerve Degeneration; Nerve Regeneration; Neuraxis; Neurophysiology - biologic function; Neuroprotective Agents; Oral; Oxidative Stress; Patient Care; Peripheral; Pharmaceutical Preparations; Population; Powder dose form; Prevention; Prevention strategy; Process; Property; Public Health; Raspberries; Rattus; Reducing Agents; Reducing diet; Reporting; Risk; Rodent Model; Services; Severities; Soldier; Stroke; Supplementation; Supportive care; Symptoms; Testing; Therapeutic; Time; Tissues; Toxic effect; Translating; Trauma; Traumatic Brain Injury; Weight; behavior test; combat; cost; design; dietary supplements; disability; effective therapy; falls; high risk; improved; motor vehicle injury; neuroinflammation; neuroprotection; peer; prevent; rehabilitation strategy; repaired; research study; therapy development

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.

描述（由申请人提供）： 创伤性脑损伤（TBI）对于美国民众和美国军人来说都是一个重大问题。与文职人员相比，在战区服役的部署人员尤其面临遭受创伤性脑损伤的风险。不同程度的爆炸伤可能导致多发伤，使 TBI 的即时治疗进一步复杂化。迄今为止，尚无临床治疗方法被证明对原发性 TBI 有效。因此，正如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疗法有望改善症状和/或减缓疾病进展。由于浆果含有高水平的抗氧化剂黄酮类化合物，特别是花青素，并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，因此它们可能有助于预防和/或治疗 TBI。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将损害降低至控制水平。此外，我们和其他人已经证明，饮食中补充适量的浆果能够抑制和改善神经炎症和神经退行性过程引起的症状。我们假设膳食补充剂中含有全冻干浆果将有效预防和治疗 TBI 的神经炎症成分。因此，我们将通过检查以下具体目标来检验这一假设： 目标 1：测试浆果粉对临床、组织学和炎症体征的影响 在损伤发生前给予浆果的 TBI 大鼠模型。目标 2：测试浆果粉对大鼠模型中临床、组织学和炎症体征的影响 症状出现后服用浆果可预防 TBI。总之，浆果的抗氧化和抗炎特性提供了一种理想的策略，因为它们易于口服，毒性低，并且可以与其他药物结合使用。开发一种口服支持疗法，成本低、易于耐受，但没有现有疗法的副作用，将大大改善 TBI 患者的护理。 公共卫生相关性： TBI 可能占所有战斗伤害的 1/3。尽管许多士兵似乎在几个月内就从轻度创伤性脑损伤中恢复过来，但仍有 10% 至 15% 的士兵表示多年来一直存在认知困难。最初的后续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的严重程度和长期残疾。浆果含有高含量的抗氧化剂黄酮类化合物，具有有益的免疫调节和抗炎特性，可能有助于预防和/或治疗 TBI。它们易于口服，毒性低，可以与其他药物联合使用。开发一种低成本、口服、易于耐受且副作用低的辅助疗法将极大地改善暴露于或患有 TBI 的患者的护理。