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

项目摘要/摘要 美国每年发生数以百万计的脑震荡，目前根据临床诊断和治疗 判断，这在很大程度上取决于患者对症状的自我报告。有很大的必要来确定 目的生物标记物增强目前诊断脑震荡和识别高危患者的临床工具 以延长康复时间。这项建议的目的是确定脑震荡对血液的影响 炎症标志物，并确定这些标志物是否有助于区分脑震荡患者和对照组 并预测脑震荡后的长期恢复。中心假设是1)早期急性后遗症- 损伤后炎性标志物的增加将改善脑震荡患者与对照组的区别 相对于传统的脑损伤标志物，2)损伤后炎症标志物将预测脑损伤的时间进程 脑震荡后的临床和神经生理恢复。为了检验我们的假设，我们将利用收集到的 NCAA-国防部震荡评估、研究和教育(CARE)的生物谱和数据 一项调查NCAA学生脑震荡自然病史的大型前瞻性研究-- 运动员和军校学员。根据OUR选择的外周炎症标志物水平 初步数据将根据CARE运动员和患有脑震荡的学员现有的等量血清进行量化 在伤前探视和几次伤后探视中。受伤后护理探视包括两个急性时间点(即 受伤后6小时和24-48小时)，即个人不再报告症状的时间点，以及七天 在重返赛场之后。配对接触性运动运动员、非接触性运动运动员和军校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、神经成像和脑损伤血液。 生物标志物数据。我们将解决以下具体目标：目标1)前瞻性地描述时间进程 运动员和学员脑震荡前后外周炎症标志物的变化 非损伤对照，目的2)确定外周炎症标志物与 运动员和MSA成员脑震荡后的症状和神经影像相关恢复指标。 探索性假设将确定性激素和性激素在这些方面的潜在缓和作用 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 在一个大规模、特征广泛的男女运动员队列中的血液炎症标志物和 学员们。这项工作还将确定基于血液的炎症标志物作为补充的用途 脑震荡的诊断和预后标志物与脑损伤标志物和其他 临床措施。

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.