Behavioral- and bio-markers of subconcussion with controlled human head impact

该项目的长期目标是确定重复的亚临床脑应激可能导致的 临床上显著的脑损伤，并利用这些知识，以防止累积的神经 残疾。亚脑震荡是一种认识不足的现象，其中颅骨撞击不会导致 临床症状，但如果频繁重复，可能会导致可测量的神经功能障碍， 运动员和其他从事活动的人会给大脑带来轻微的机械压力。之甚少 在这些情况下，我们知道脑组织损伤如何在细胞水平上发展和解决， 没有任何一次单独的身体创伤足以引起外界可见的 脑震荡症状这种亚震荡打击经常发生在正常发挥的过程中 （足球中的拦网、足球中的头球等）。然而，没有明显的临床症状， 神经系统损伤被忽视，球员返回比赛，损伤会随着时间的推移而积累。 拟议的项目是基于这样一个前提，即轻微的机械冲击会引起大脑压力 无法通过自我检查或普通诊断观察到，但可以通过专门的行为检测到 测试和尖端的细胞外囊泡分析技术。这些技术可以确定 当它是安全的或危险的恢复活动。利用足球头球诱导轻度机械性 强调脑组织，我们已经建立了一个创新的人类实验范式， 指示在体育/娱乐活动期间通常经历的压力水平。与此 范例，我们将开发新的工具来表征亚震荡冲击的神经影响。 在目标1中，我们将使用姿势的敏感测量来量化轻度头部撞击的行为影响。 站立和行走时的稳定性。在目标2中，我们将确定一种循环分子模式， 亚脑震荡性脑损伤使用血脑屏障和中枢神经系统细胞衍生的创新技术 微囊泡分析。在目标3中，我们将识别亚震荡头部的独特microRNA特征， 使用尖端测序技术对循环外泌体的影响。拟定研究 创新，因为它将引入一个全新的层面的病理生理学， 亚震荡性头部撞击该项目的结果将可能导致创新的发展， 行为和分子诊断工具，以评估累积性脑损伤的风险。

The long-term goals of this project are to determine how repeated, subclinical brain stress may lead to clinically significant brain damage, and to use this knowledge to prevent cumulative neurological disability. Sub-concussion is an under-recognized phenomenon, in which cranial impact does not lead to clinical symptoms, but when repeated frequently, can cause measurable neurological dysfunction in athletes and others engaged in activities that introduce mild mechanical stresses to the brain. Little is known about how brain tissue injury develops and resolves at the cellular level in these cases because no individual episode of physical trauma is sufficiently strong enough to cause outwardly observable concussion symptoms. Such sub-concussive blows occur frequently during the course of normal play (blocking in football, heading in soccer, etc.). However, without obvious clinical signs, underlying neurological damage goes unnoticed, players return to play and damage can accumulate over time. The proposed project is based on the premise that mild mechanical impact introduces brain stress unobservable by self-examination, or common diagnostics, but detectable by specialized behavioral tests and cutting-edge extracelluar vesicle analysis techniques. Such techniques could determine when it is safe or dangerous to resume the activity. Using soccer heading to induce mild mechanical stress on brain tissue, we have established an innovative human experimental paradigm that is indicative of commonly experienced stress levels during sports/recreational activities. With this paradigm, we will develop new tools to characterize the neurological effects of sub-concussive impact. In Aim 1, we will quantify behavioral effects of mild head impact using sensitive measures of postural stability during standing and walking. In Aim 2, we will determine a circulating molecular pattern of subconcussive head injury using an innovative technique for blood brain barrier- and CNS cell-derived microvesicle profiling. In Aim 3, we will identify a unique microRNA signature of subconcussive head impact in circulating exosomes using cutting-edge sequencing technology. The proposed study is innovative because it will introduce an entirely new dimension to the pathophysiology of subconcussive head impact. Results of this project will potentially lead to the development of innovative behavioral and molecular diagnostic tools to assess risk of cumulative brain injury.