Impact of Aging on the Immune Response to Traumatic Brain Injury

描述（由申请人提供）：创伤性脑损伤（TBI）在老年人中很常见，占美国每年脑损伤的25%以上，具有相当大的死亡率、长期损伤和残疾。与患有类似损伤的年轻人相比，患有TBI的老年人的结果更糟。治疗老年人创伤性脑损伤的临床努力并没有在身体损伤、残疾和健康相关的生活质量方面取得预期的改善。管理的一个关键障碍 TBI的一个重要问题是，对老化导致的TBI反应的潜在差异以及老年如何影响TBI后的病理学和恢复的知识有限。本申请提出使用一组新的免疫生物标志物来增强对从TBI恢复的轨迹以及负责TBI后老年人中的慢性症状、损伤和健康相关生活质量下降的潜在机制的认识。我们提出，老化是一个生物学因素，有助于通过调节TBI的免疫反应，损伤的病理反应，并将测试这一假设使用一种新的模型的损伤和残疾。这项前瞻性队列研究的目的是：1）比较有和没有轻度TBI的年轻人和老年人在损伤后6个月内的细胞免疫应答、血浆炎症生物标志物浓度以及损伤、残疾和健康相关生活质量的测量（每组75个）和2）确定所选细胞免疫和血浆生物标志物与损伤之间的关联，轻度TBI老年人伤后3个月和6个月的残疾和健康相关生活质量。 公共卫生相关性：老年人创伤性脑损伤（TBI）是一个重要的临床公共卫生问题，占美国每年TBI的25%以上。老年人TBI后的功能和生活质量结果与具有类似损伤的年轻人相比较差，并且在老年人中治疗TBI的努力并未产生预期的结果改善。在这个建议中，我们试图解释这一点的生物学原理，并确定可能的治疗目标，通过测试的假设，即较差的结果与老年人TBI后免疫反应的改变有关。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) in older adults is common, accounting for over 25% of brain injuries in the US each year, with considerable mortality, long-term impairment and disability. Outcomes among older adults with TBI are disparately worse when compared to their younger counterparts with similar injuries. Clinical efforts to treat TBI in older adults have not yielded the expected improvements in physical impairment, disability and health- related quality of life. A critical barrier to the management of TBI is that there is limited knowledge about potential differences in the response to TBI that results from aging, and how older age may affect pathology and recovery following TBI. The current application proposes to use a novel set of immune biomarkers to enhance knowledge of the trajectory of recovery from TBI and the underlying mechanisms responsible for chronic symptoms, impairment and decrements in health-related quality of life in older adults following TBI. We propose that aging is a biological factor that contributes to the pathological response to injury by modulating the immune response to TBI and will test this hypothesis using a novel model of impairment and disability. The aims of this prospective cohort study are to: 1) Compare cellular immune responses, plasma inflammatory biomarker concentrations, and measures of impairments, disability and health-related quality of life up to 6 months post-injury in young and older adults with and without mild TBI (75 per group) and 2) Determine the association between selected cellular immune and plasma biomarkers and impairments, disability and health- related quality of life at 3 and 6 months post-injury in older adults with mild TBI. PUBLIC HEALTH RELEVANCE: Traumatic brain injury (TBI) in the elderly is a major and important clinical public health issue, accounting for more than 25% of TBIs the US each year. Functional and quality of life outcomes following TBI among older adults are poorer compared to younger counterparts with similar injuries and efforts to treat TBI in older adults have not yielde expected improvements in outcome. In this proposal we seek to explicate the biological rationale for this, and identify targets for possible treatment by testing the hypothesis that poorr outcomes are related to an altered immune response following TBI in the older adult.