Detecting Axonal Damage After Mild Traumatic Brain Injury

描述（由申请人提供）：该多学科项目的长期目标是了解轴突损伤、血脑屏障（BBB）损伤和人血清蛋白质组之间的关系，作为鉴定准确的轻度创伤性脑损伤（轻度TBI）血清标志物的先决条件。这样一个标志是至关重要的发展战略，以减少残疾的这种伤害。目前建议的关键基本假设是轴突损伤是轻度TBI后神经功能障碍的结构基质。磁共振成像的动态形式扩散张量成像（DTI）的最新发展，现在使检测人类大脑中的轴突损伤成为可能。将聚集37名轻度TBI受试者和37名年龄和性别匹配的骨科对照组，以验证DTI作为临床显著轴突损伤的测量，确定轴突损伤和BBB损伤之间的关系，并使用血清蛋白质组学分析鉴定轻度TBI后轴突损伤特有的蛋白质。临床结果将通过神经行为功能、脑震荡后症状和生活质量进行评估。具体目标：1。分别于伤后12 h、1周、4周行DTI检查，并与常规MRI及血清S-100 B进行比较，分析DTI检测轴索损伤的临床意义。2.识别轻度TBI后的BBB损伤，并与轴突损伤和临床结局相关。3.使用SELDI蛋白芯片分析交换分级血清，鉴定轻度TBI后轴突损伤特有的血清蛋白。在奖励期结束时，我们将准备在一个单独的队列中验证推定的轻度TBI血清标志物，然后再开发用于临床的强化检测方法。轻度TBI在美国是一个重要的公共卫生问题，目前没有客观的诊断帮助和治疗。这种伤害不仅每年影响120万美国人，而且经常影响在国外参与作战行动的美国士兵和在恐怖袭击中幸存下来的公共安全人员。简单反应时间和其他认知功能的紊乱会干扰这些人必须履行的重要职责，使自己和他人处于危险之中。开发一种快速诊断轴突损伤的方法不仅是开发未来疗法的必要先决条件，而且对于确定这些关键个体履行其关键职责的能力至关重要。

DESCRIPTION (provided by applicant): The long-term goal of this multidisciplinary project is to understand the relationship between axonal injury, blood brain barrier (BBB) damage and the human serum proteome as a prerequisite to the identification of an accurate mild traumatic brain injury (mild TBI) serum marker. Such a marker is vital to the development of strategies to reduce the disabilities from this injury. The key underlying assumption of the current proposal is that axonal injury is the structural substrate behind post-mild TBI neurologic dysfunction. The recent development of diffusion tensor imaging (DTI), a dynamic form of MRI, now makes possible the detection of axonal injury in the human brain. A cohort of 37 mild TBI subjects and 37 age and gender-matched orthopedic controls will be assembled to validate DTI as a measure of clinically significant axonal injury, determine the relationship between axonal injury and BBB damage, and identify proteins unique to axonal injury after mild TBI using proteomic analysis of serum. Clinical outcomes will be assessed by neurobehavioral functioning, post-concussive symptoms and quality of life. Specific Aims: 1. Compare DTI to conventional MRI and serum S-100B at 12 hours, 1 week and 4 weeks post-injury, and determine the clinical significance of the axonal injury detected. 2. Identify BBB damage after mild TBI and relate to axonal injury and clinical outcome. 3. Identify serum proteins unique to axonal injury after mild TBI using SELDI protein chip analysis of exchange-fractionated serum. At the conclusion of the award period, we will be poised to validate putative mild TBI serum markers in a separate cohort, prior to the development of hardened assays for clinical use. Mild TBI is an important public health problem in the US for which there is currently no objective diagnostic aid and no treatment. Not only does this injury affect 1.2 million Americans annually, it also frequently affects US soldiers involved in combat operations abroad and public safety personnel who survive terrorist attacks. Disturbances in simple reaction time and other cognitive functions can interfere with the important duties these individuals must perform, putting themselves and others at risk. The development of a rapid means of diagnosing axonal injury is not only a necessary prerequisite to the development of future therapies, it is essential to determining the ability of these key individuals to perform their critical duties.