Detecting Axonal Damage After Mild Traumatic Brain Injury

描述(申请人提供)：这个多学科项目的长期目标是了解轴突损伤、血脑屏障(BBB)损伤和人类血清蛋白质组之间的关系，作为识别准确的轻度创伤性脑损伤(轻度脑损伤)血清标记物的先决条件。这一标志对于制定减少这种伤害所致残疾的战略至关重要。当前提议的关键潜在假设是，轴突损伤是轻度脑外伤后神经功能障碍的结构性基础。扩散张量成像(DTI)是磁共振成像的一种动态形式，它的最新发展使检测人脑中的轴突损伤成为可能。一个由37名轻度脑损伤受试者和37名年龄和性别匹配的骨科对照组成的队列将被聚集在一起，以验证DTI作为临床显著轴突损伤的衡量标准，确定轴突损伤与血脑屏障损伤之间的关系，并利用血清蛋白质组学分析识别轻度脑损伤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来评估。具体目的：1.在伤后12小时、1周、4周将弥散张量成像与常规磁共振及血清S-100B进行比较，确定轴索损伤的临床意义。2.确定轻度颅脑损伤后血脑屏障的损害，并与轴索损伤和临床转归相关。3.利用交换分离血清的SELDI蛋白芯片分析鉴定轻度脑损伤后轴索损伤特有的血清蛋白。在获奖期结束时，我们将准备在一个单独的队列中验证假定的轻度TBI血清标志物，然后开发用于临床的强化分析。轻度脑外伤在美国是一个重要的公共卫生问题，目前还没有客观的诊断援助和治疗方法。这种伤害不仅每年影响120万美国人，还经常影响参加海外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障碍可能会干扰这些人必须履行的重要职责，使自己和其他人处于危险之中。开发一种快速诊断轴突损伤的方法不仅是未来治疗方法发展的必要前提，而且对于确定这些关键个人履行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.