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

项目总结/摘要 美国每年发生数百万例脑震荡，目前根据临床诊断和管理。 判断，这在很大程度上是由病人的自我报告的症状。我们非常需要确定 客观的生物标志物，以加强目前的临床工具，诊断脑震荡和识别患者的风险 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个体与对照组 并预测脑震荡后的长期恢复。核心假设是：1）早期急性后- 炎症标志物的损伤增加将改善脑震荡个体与对照的区分 相对于传统的脑损伤标志物，和2）损伤后炎症标志物将预测 脑震荡后的临床和神经生理恢复。为了验证我们的假设，我们将利用收集到的 来自NCAA-DoD脑震荡评估，研究和教育（CARE）的生物标本和数据 财团研究，一项大型的前瞻性研究，调查NCAA学生脑震荡的自然史， 运动员和军校学员。外周水平的炎症标志物选择的基础上，我们 初步数据将从CARE运动员和脑震荡学员的现有血清等分试样中进行量化 在受伤前和几次受伤后的访问中。CARE损伤后访视包括两个急性时间点（即，内 6-小时和受伤后24-48小时），个人不再报告症状的时间点，以及7天 回到游戏中。匹配的接触性运动运动员，非接触性运动员，和学员完成类似的 访问并将作为对照。分析将纳入现有的临床、神经影像学和脑损伤血液 生物标记数据。我们将讨论以下具体目标：目标1）时间进程的特征 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）确定外周炎性标志物与 运动员和MSA成员脑震荡后恢复症状和神经影像学相关指标。 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， 在一个大型的，广泛特征化的男性和女性运动员队列中， 童子军活动的啊这项工作还将确定血液为基础的炎症标记物作为补充的效用 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.