Peripheral inflammatory biomarkers for acute concussion: An extension of the Concussion Assessment, Research and Education Consortium Study

急性脑震荡的外周炎症生物标志物：脑震荡评估、研究和教育联盟研究的延伸

• 批准号: 10037999
• 负责人: Timothy B. Meier
• 金额: $ 44.41万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10037999
• 关键词: Academy; Acute; Address; Affect; Aliquot; Assessment tool; Biological Markers; Blood; Brain; Brain Concussion; Brain Injuries; Clinical; Clinical Management; Data; Diagnosis; Diagnostic; Diffusion; Discrimination; Education; Functional disorder; Future; Glial Fibrillary Acidic Protein; Gonadal Steroid Hormones; Hour; Image; Individual; Inflammatory; Injury; Judgment; Knowledge; Light; Link; Magnetic Resonance Imaging; Manufactured football; Measures; Military Personnel; Modeling; National Institute of Neurological Disorders and Stroke; Natural History; Neurocognitive; Neurofilament-L; Outcome; Patient Self-Report; Patients; Peripheral; Play; Population; Prognostic Marker; Prospective Studies; Protocols documentation; Public Health; Publishing; Recovery; Reporting; Research; Risk; Serum; Services; Site; Sports; Structure; Symptoms; Testing; Time; Visit; Woman; Work; base; biomarker panel; blood-based biomarker; clinical predictors; cohort; cost effectiveness; design; diagnostic biomarker; follow-up; improved; indexing; inflammatory marker; injured; injury burden; innovation; interest; member; men; neurofilament; neuroimaging; neuroimaging marker; neuropathology; neurophysiology; point of care; prognostic value; prospective; relative cost; student athlete; tau Proteins; tool; ubiquitin C-terminal hydrolase

Project Summary/Abstract Millions of concussions occur annually in the US and are currently diagnosed and managed based on clinical judgment, which is largely informed by a patient’s self-report of symptoms. There is a great need to identify objective biomarkers to augment current clinical tools for diagnosing concussion and identifying patients at risk for prolonged recovery. The objectives of this proposal are to determine the effects of concussion on blood markers of inflammation and establish if these markers can help discriminate concussed individuals from controls and predict prolonged recovery following concussion. The central hypotheses are 1) that an early-acute post- injury increase in inflammatory markers will improve the discrimination of concussed individuals from controls relative to traditional brain injury markers, and 2) post-injury inflammatory markers will predict the time course of clinical and neurophysiological recovery following concussion. To test our hypotheses, we will leverage collected biospecimens and data from the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium Study, a large, prospective study investigating the natural history of concussion in NCAA student- athletes and military service academy cadets. Peripheral levels of inflammatory markers selected based on our preliminary data will be quantified from existing aliquots of serum in CARE athletes and cadets with concussion at pre-injury visits and several post-injury visits. CARE post-injury visits include two acute time points (i.e., within 6-hours and 24-48 hours post-injury), the point at which individuals no longer report symptoms, and seven days following return-to-play. Matched contact sport athletes, non-contact sport athletes, and cadets complete similar visits and will serve as controls. Analyses will incorporate existing clinical, neuroimaging, and brain injury blood biomarker data. We will address the following specific aims: Aim 1) Prospectively characterize the time course of changes in peripheral markers of inflammation from pre- to post-concussion in athletes and cadets relative to non-injured controls, Aim 2) Determine the extent to which peripheral inflammatory markers are associated with symptom and neuroimaging-related indices of recovery following concussion in athletes and MSA members. Exploratory hypotheses will determine the potential moderating effects of sex and sex hormones on these markers and outcomes. This work is significant because it will prospectively determine the effects of concussion on blood markers of inflammation in a large, extensively characterized cohort of men and women athletes and cadets. This work will also determine the utility of blood-based inflammatory markers as complementary diagnostic and prognostic markers for concussion to be used in conjunction with brain injury markers and other clinical measures.

项目概要/摘要 美国每年发生数百万起脑震荡，目前是根据临床诊断和治疗的 判断，很大程度上取决于患者的症状自我报告。非常有必要去识别 客观的生物标记物可增强当前诊断脑震荡和识别高危患者的临床工具 为了延长恢复时间。该提案的目的是确定脑震荡对血液的影响 炎症标记物，并确定这些标记物是否可以帮助区分脑震荡个体和对照组 并预测脑震荡后的长期恢复。中心假设是 1）早期急性后 炎症标记物的损伤增加将改善脑震荡个体与对照组的区别 相对于传统的脑损伤标记物，2）损伤后炎症标记物将预测脑损伤的时间进程 脑震荡后的临床和神经生理学恢复。为了检验我们的假设，我们将利用收集到的 来自 NCAA-DoD 脑震荡评估、研究和教育 (CARE) 的生物样本和数据 联盟研究是一项大型前瞻性研究，调查 NCAA 学生脑震荡的自然史 运动员和军事学院学员。根据我们的选择的炎症标志物的外周水平 初步数据将从 CARE 脑震荡运动员和学员的现有等份血清中进行量化 在受伤前的访视和几次受伤后的访视中。 CARE 受伤后就诊包括两个急性时间点（即，在 受伤后 6 小时和 24-48 小时），即个人不再报告症状的时间点，以及 7 天 恢复比赛后。匹配的接触式运动运动员、非接触式运动运动员和学员完成类似的任务 访问并将作为控制。分析将结合现有的临床、神经影像和脑损伤血液 生物标志物数据。我们将实现以下具体目标： 目标 1) 前瞻性地描述时间进程 运动员和学员从脑震荡前到脑震荡后的外周炎症标志物相对于 未受伤对照，目标 2) 确定外周炎症标志物与 运动员和 MSA 会员脑震荡后恢复的症状和神经影像相关指标。 探索性假设将确定性和性激素对这些的潜在调节作用 标记和结果。这项工作意义重大，因为它将前瞻性地确定脑震荡的影响 对一大群具有广泛特征的男女运动员的炎症血液标志物进行研究 学员。这项工作还将确定基于血液的炎症标记物作为补充的效用 脑震荡的诊断和预后标记物与脑损伤标记物和其他标记物结合使用 临床措施。

项目成果

Increased brain age and relationships with blood-based biomarkers following concussion in younger populations.

• DOI: 10.1007/s00415-023-11931-8
• 发表时间: 2023-12
• 期刊: JOURNAL OF NEUROLOGY
• 影响因子: 6
• 作者: Mayer, Andrew R.;Meier, Timothy B.;Ling, Josef M.;Dodd, Andrew B.;Brett, Benjamin L.;Robertson-Benta, Cidney R.;Huber, Daniel L.;Van der Horn, Harm J.;Broglio, Steven P.;McCrea, Michael A.;McAllister, Thomas
• 通讯作者: McAllister, Thomas