Detecting Axonal Damage After Mild Traumatic Brain Injury

检测轻度创伤性脑损伤后的轴突损伤

• 批准号: 7264306
• 负责人: JEFFREY John BAZARIAN
• 金额: $ 54.99万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-20 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7264306
• 关键词: Affect; Age; American; Anisotropy; Award; Axonal Transport; Biological Assay; Blood - brain barrier anatomy; Brain; Brain Injuries; Calcium; Clinical; Cognitive deficits; Data; Detection; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Disruption; Event; Funding; Future; Gender; Goals; Hour; Human; Human Resources; Image; Individual; Injury; Knowledge; Lesion; Magnetic Resonance Imaging; Measures; Methods; Microtubules; Molecular; Motion; Neurologic Dysfunctions; Operative Surgical Procedures; Orthopedics; Outcome; Patients; Pattern; Positioning Attribute; Post-Concussion Syndrome; Prealbumin; Process; Protein Microchips; Proteins; Proteome; Proteomics; Public Health; Quality of life; Reaction Time; Relative (related person); Research Personnel; Risk; Safety; Sampling; Score; Serum; Serum Markers; Serum Proteins; Signs and Symptoms; Soldier; Stretching; TBI Patients; Technology; Traumatic Brain Injury; Validation; Water; Week; Western Blotting; base; clinically significant; cognitive function; cohort; design; disability; multidisciplinary; neurobehavioral; neurobehavioral test; neuroimaging; programs; surface enhanced laser desorption ionization

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.

描述（由申请人提供）：这个多学科项目的长期目标是了解轴突损伤、血脑屏障（BBB）损伤和人血清蛋白质组之间的关系，作为准确识别轻度创伤性脑损伤的先决条件（轻度 TBI）血清标记物。这样的标记对于制定减少这种伤害造成的残疾的策略至关重要。当前提议的关键基本假设是轴突损伤是轻度 TBI 后神经功能障碍背后的结构基础。扩散张量成像 (DTI)（MRI 的一种动态形式）的最新发展现在使得检测人脑中的轴突损伤成为可能。将组装一组由 37 名轻度 TBI 受试者和 37 名年龄和性别匹配的骨科对照者组成的队列，以验证 DTI 作为临床显着轴突损伤的衡量标准，确定轴突损伤与 BBB 损伤之间的关系，并识别轻度 TBI 后轴突损伤特有的蛋白质。 TBI 使用血清蛋白质组学分析。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。具体目的： 1. 将损伤后 12 小时、1 周和 4 周的 DTI 与常规 MRI 和血清 S-100B 进行比较，并确定检测到的轴突损伤的临床意义。 2. 识别轻度 TBI 后的 BBB 损伤，并与轴突损伤和临床结果相关。 3. 使用交换分级血清的 SELDI 蛋白芯片分析，鉴定轻度 TBI 后轴突损伤特有的血清蛋白。在奖励期结束时，我们将准备在单独的队列中验证假定的轻度 TBI 血清标志物，然后再开发用于临床使用的强化检测方法。轻度 TBI 是美国的一个重要公共卫生问题，目前尚无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，还经常影响到参与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紊乱可能会干扰这些人必须履行的重要职责，使自己和他人面临风险。开发诊断轴突损伤的快速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人员履行其关键职责的能力也至关重要。