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，血液脑屏障（BBB）损伤与人血清蛋白质组之间的关系，作为确定准确的轻度创伤性脑损伤（轻度TBI）的先决条件。这样的标记对于制定减少这种伤害残疾的战略至关重要。当前建议的关键基础假设是轴突损伤是后TBI神经功能障碍背后的结构底物。现在，MRI的动态形式的扩散张量成像（DTI）的最新发展使得可以检测到人脑中的轴突损伤。将组装37名轻度TBI受试者和37个年龄和性别匹配的骨科对照组，以验证DTI，以衡量临床上显着的轴突损伤，确定轴突损伤与BBB损伤之间的关系，并鉴定使用蛋白质体分析后，轴突损伤与轴突损伤所特有的蛋白质与轴突损伤所特有的蛋白质。临床结果将通过神经行为功能，脑后症状和生活质量来评估。具体目的：1。将DTI与传统的MRI和血清S-100B进行比较，并在受伤后12小时1周和4周，并确定检测到的轴突损伤的临床意义。 2。在轻度TBI后确定BBB损伤，并与轴突损伤和临床结局有关。 3。使用SELDI蛋白质芯片分析交换式血清，鉴定轻度TBI后轴突损伤特有的血清蛋白。在奖励期结束时，我们将准备在开发硬化的测定法以供临床使用之前，在单独的队列中验证推定的轻度TBI血清标记。轻度TBI是美国目前没有客观诊断援助且没有治疗的重要公共卫生问题。这种伤害不仅会影响每年120万美国人，而且还经常影响参与国外战斗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干扰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。诊断轴突损伤的快速方法的发展不仅是未来疗法发展的必要先决条件，而且必须确定这些关键人物履行其关键职责的能力。