Validation of Putative Serum of Axonal Damage After Mild TBI

轻度 TBI 后轴突损伤推定血清的验证

• 批准号: 8814120
• 负责人: JEFFREY John BAZARIAN
• 金额: $ 15.69万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8814120
• 关键词: Address; Affect; Afghanistan; Albumins; American; Anisotropy; Apolipoprotein A-I; Apolipoproteins; Award; Biochemical; Blood; Brain; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Characteristics; Clinical; Clinical Investigator; Cognitive deficits; Conflict (Psychology); DNA; DNA Damage; DNA Methylation; Diagnostic; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Epigenetic Process; Functional disorder; Generations; Goals; Gold; Histone Acetylation; Histones; Image; Injury; Investigation; Iraq; Learning; Leukocytes; Link; Lipids; Measures; Mentors; Methylation; Mid-Career Clinical Scientist Award (K24); Nerve Degeneration; Neurologic Dysfunctions; Pattern; Performance; Peripheral; Permeability; Process; Proteins; Public Health; Recovery; Regulation; Research; Research Personnel; Research Project Grants; Research Support; Risk; Role; Sampling; Serum; Serum Markers; Sports; Structure; Swelling; TBI Patients; Testing; Thinking; Time; Training; Traumatic Brain Injury; Validation; Ventricular; Ventriculostomy; axon injury; brain cell; career development; cell injury; circulating DNA; clinical care; cognitive function; cognitive performance; cognitive testing; cohort; college; differential expression; experience; improved; injured; insight; interest; meetings; mild traumatic brain injury; motor deficit; neurofilament; neuropathology; patient oriented research; prevent; public health relevance; response; standard measure; therapy development

DESCRIPTION (provided by applicant): Research Goals: To examine putative protein markers of traumatic axonal injury (AI) in order to elucidate the neuropathology of mild traumatic brain injury (mild TBI) and its sequelae. Career Development Goals: To provide adequate time to mentor new clinical investigators and perform patient-oriented research in TBI. Research Project: Axonal injury is thought to be the pathophysiological process that underlies the cognitive and motor deficits found after mild TBI. The central hypothesis of this proposal is that axonal injury results in the differential expression of serum and cerebrospinal fluid (CSF) proteins and that examination of these proteins can provide insight into the mechanism of axonal injury. The goal of this project is to examine alterations in blood and CSF to test several hypotheses related to the biochemical and cellular response to mild TBI. This goal will be accomplished through two investigative strategies: 1) Analysis of the exposure characteristic of serum and CSF proteins; and 2) Correlation of protein markers of axonal damage to changes in axonal structure on diffusion tensor imaging (DTI) and cognitive function. Specifically, this project seeks to determine the putative role of a marker of neurofilament damage (pNFH) and a marker of lipid regulation (ApoA1) in axonal injury after mild TBI. The potential link between mild TBI and the increased long-term risk of neurodegeneration will be explored by an analysis of epigenetic changes in the DNA of circulating leukocytes. To address these aims the PIs propose to assemble a cohort of college athletes participating in contact sports in which mild TBI is a known risk, and a cohort of moderate to severe TBI patients who have an external ventriculostomy drain placed as a part of their clinical care. Because this study involves the investigation of several aspects of brain structure and function after mild, moderate and severe TBI, it serves as an ideal platform for the mentoring of new clinical investigators interested in traumatic brain injury. This proposal meets the goals of the K24 award by 1) demonstrating the need for the PI to devote more time to and to augment his research capabilities, and by 2) providing the ideal conditions under which new clinical investigators can be mentored in the conduct of Patient-Oriented Research. PUBLIC HEALTH RELEVANCE: Mild TBI is an important public health problem in the US for which there is currently no objective diagnostic aid and no treatment. This injury affects over 1.2 million Americans annually and is the signature injury of the conflicts in Iraq and Afghanistan. Mild TBI can result in problems of thinking and performing daily activities that can last from months to years. The process by which brain cells are damaged and how this damage is linked to brain dysfunction is incompletely understood. This has prevented the development of treatments that could improve the lives of those injured. The PIs propose to examine changes in the blood and spinal fluid to learn more about mild TBI. In the process they hope to train and inspire a new generation of clinical researchers interested in traumatic brain injury.

描述（由申请人提供）：研究目标：检查创伤性轴突损伤（AI）的假定蛋白质标志物，以阐明轻度创伤性脑损伤（轻度TBI）及其后遗症的神经病理学。职业发展目标：提供足够的时间来指导新的临床研究人员并在TBI中进行以患者为导向的研究。研究项目：轴突损伤被认为是在轻度TBI后发现的认知和运动不足的基础的病理生理过程。该提议的中心假设是轴突损伤会导致血清和脑脊液（CSF）蛋白的差异表达，并且对这些蛋白质的检查可以提供对轴突损伤机理的见解。该项目的目的是检查血液和CSF的变化，以检验与温和TBI的生化和细胞反应有关的几种假设。该目标将通过两种调查策略来实现：1）分析血清和CSF蛋白的暴露特征； 2）轴突损伤的蛋白质标志物与扩散张量成像（DTI）和认知功能上轴突结构变化的变化的相关性。具体而言，该项目旨在确定轻度TBI后轴突损伤中神经丝损伤（PNFH）标记（PNFH）和脂质调节标记的推定作用。通过对循环白细胞DNA的表观遗传变化的分析，将探索轻度TBI与长期神经退行性风险增加之间的潜在联系。 为了解决这些目的，PIS建议组装一群参加接触运动的大学运动员，其中轻度TBI是已知的风险，以及一组中度至重度的TBI患者，这些患者将其作为临床护理的一部分放置在外部心室造口术。由于这项研究涉及对轻度，中度和重度TBI后大脑结构和功能的几个方面进行研究，因此它是指导对创伤性脑损伤感兴趣的新临床研究人员的理想平台。 该提案符合K24奖的目标1）表明PI需要更多时间用于并增强其研究能力，并由2）提供理想的条件，在这些条件下，可以在这些条件下进行新的临床研究人员进行以患者为导向的研究。 公共卫生相关性：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。这种伤害每年影响超过120万美国人，是伊拉克和阿富汗冲突的签名伤害。轻度的TBI可能会导致思维和进行日常活动的问题，这些活动可以持续数月到几年。脑细胞受损的过程以及如何将这种损伤与脑功能障碍相关联。这阻止了可以改善受伤者生命的治疗的发展。 PI建议检查血液和脊髓液的变化，以了解有关轻度TBI的更多信息。在此过程中，他们希望训练和激发新一代对脑损伤感兴趣的临床研究人员。