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Physiological mechanisms of a biomarker of recovery from concussion

脑震荡恢复生物标志物的生理机制

基本信息

批准号：
9902561
负责人：
JOHN Joseph LEDDY
金额：
$ 34.89万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902561
关键词：
Accidents Adolescent Affect American Autonomic nervous system Biological Markers Blood Blood Pressure Blood flow Brain Brain Concussion Brain Injuries Brain Stem Buffaloes Carbon Dioxide Cardiac Cardiac Output Cardiovascular system Cells Cerebrovascular Circulation Cerebrum Characteristics Clinical Communication Corpus Callosum Development Diagnosis Diagnostic Differential Diagnosis Exercise Exercise Physiology Exercise Test Exercise Tolerance Female Financial compensation Goals Gold Guidelines Head-Down Tilt Heart Heart Rate Image Individual Injury Lactates Low Cardiac Output Lung Magnetic Resonance Imaging Measures Mediating Metabolic dysfunction Methods Military Personnel Monitor Muscle Nervous System Physiology Nervous System Trauma Participant Patients Perfusion Peripheral Physicians Physiological Physiology Post-Concussion Syndrome Proxy Pulse Pressure Recovery Research Resolution Rest Role Serum Services Source Specificity Speed Spin Labels Sports Stroke Volume Symptoms Testing Treadmill Tests Work Workload base brain abnormalities concussive symptom exercise intolerance experience improved innovation male novel patient subsets public health relevance response return to sport specific biomarkers treadmill ventilation white matter white matter injury

项目摘要

DESCRIPTION (provided by applicant): Each year millions of Americans are concussed from sport-related incidents, accidents or military service. While extensive research has been done to identify biomarkers for diagnosing concussion, a specific biomarker for concussion recovery has yet to be identified. Concussion is a brain injury with physiological effects on cerebral blood flo (CBF) and autonomic nervous system (ANS) function. These effects may be why exercise exacerbates concussion symptoms. Thus, exercise intolerance is a physiological sign of concussion. Ergo, normal exercise tolerance indicates physiological recovery. Our long-term goal is to better understand the systemic physiological disturbance of concussion to develop reliable methods for the differential diagnosis of concussion and of post-concussion syndrome, to establish objective markers of recovery, and to develop novel treatments to speed recovery. The overall objective of this application is to identify the physiological mechanisms of exercise intolerance in concussion. The rationale for the proposed study is that our work could show that systematic determination of return of exercise tolerance is a specific biological marker of recovery from concussion. This would help patients and clinicians know with confidence when it is safe to return to activity. We developed the Buffalo Concussion Treadmill Test to systematically evaluate exercise tolerance in concussed athletes. We have found abnormally elevated CBF during exercise after concussion in association with altered sensitivity to the effects of CO2 that blunts ventilation. We have also detected that cardiac output (CO) is low after concussion. A fundamental question is whether exercise tolerance after concussion is limited centrally (brain) or peripherally (cardiovascular/muscle). We will examine this by pursuing the following two specific aims: (1) Identify the source (central or peripheral) of exercise intolerance in concussion and (2) Identify the mechanism of central exercise intolerance in concussion. Concussed male and female participants will have measures of CO2 sensitivity, ventilation, CBF (by arterial spin labelling in the MRI), blood lactate, and CO at res and during simulated exercise (head down tilt, HDT) in the MRI machine and during the Buffalo treadmill exercise test soon after concussion and upon recovery. We will also measure DTI to evaluate for injury to the brainstem and corpus callosum. Values will be compared to those in healthy controls. The work is expected to identify that the physiological mechanism of exercise intolerance in concussion is central from abnormal control of CBF. The work is expected to establish that return of normal physiology (and of normal exercise tolerance) is a functional biomarker of recovery from concussion. The work is significant because a physiological biomarker will impact how patients are judged clinically to be recovered from concussion, i.e., physiologically ready to return to sport, work and military duty. Our work is innovative because we are using exercise intolerance as a clinical measure of abnormal physiological control of CBF as a result of concussion.

描述（由申请人提供）：每年有数百万美国人因运动相关事件，事故或兵役而脑震荡。虽然已经进行了广泛的研究来确定诊断脑震荡的生物标志物，但尚未确定脑震荡恢复的特定生物标志物。脑震荡是一种对脑血流（CBF）和自主神经系统（ANS）功能产生生理性影响的脑损伤。这些影响可能就是为什么运动会加剧脑震荡症状。因此，运动不耐症是脑震荡的一个生理信号。因此，正常的运动耐力表明生理恢复。我们的长期目标是更好地了解脑震荡的全身生理障碍，开发脑震荡和脑震荡后综合征的鉴别诊断的可靠方法，建立恢复的客观标志物，并开发新的治疗方法来加速恢复。本申请的总体目标是确定脑震荡中运动不耐受的生理机制。这项研究的基本原理是，我们的工作可以表明，系统测定运动耐量的恢复是脑震荡恢复的一个特定生物标志。这将有助于患者和临床医生有信心地知道什么时候可以安全地恢复活动。我们开发了布法罗震荡跑步机试验，以系统地评估脑震荡运动员的运动耐量。我们发现脑震荡后运动时CBF异常升高与对CO2影响的敏感性改变有关，CO2影响通气。我们还检测到脑震荡后心输出量（CO）降低。一个基本的问题是脑震荡后的运动耐量是否受到中枢（大脑）或外周（心血管/肌肉）的限制。我们将通过以下两个具体目标来研究这一点：（1）确定脑震荡运动不耐受的来源（中枢或外周）和（2）确定脑震荡中枢运动不耐受的机制。脑震荡的男性和女性参与者将在静止时和MRI机器中模拟运动（头低位倾斜，HDT）期间以及脑震荡后不久和恢复后的布法罗跑步机运动测试期间测量CO2敏感性、通气量、CBF（通过MRI中的动脉旋转标记）、血乳酸和CO。我们还将测量DTI以评估脑干和胼胝体的损伤。将数值与健康对照组的数值进行比较。这项工作有望确定脑震荡运动不耐受的生理机制是CBF控制异常的核心。这项工作预计将确定恢复正常的生理（和正常的运动耐力）是从脑震荡中恢复的功能生物标志物。这项工作意义重大，因为生理生物标志物将影响临床上如何判断患者从脑震荡中恢复，即，在生理上准备好重返运动、工作和军事任务。我们的工作是创新的，因为我们正在使用运动不耐症作为脑震荡导致的CBF异常生理控制的临床措施。