Physiological mechanisms of a biomarker of recovery from concussion

脑震荡恢复生物标志物的生理机制

• 批准号: 9402900
• 负责人: JOHN Joseph LEDDY
• 金额: $ 5万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402900
• 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; Environmental air flow; Exercise; Exercise Physiology; Exercise Tolerance; Exercise stress test; Female; Financial compensation; Functional disorder; Goals; Gold; Guidelines; Head-Down Tilt; Heart Rate; Image; Individual; Injury; Lactates; Low Cardiac Output; Lung; Magnetic Resonance Imaging; Measures; Mediating; Metabolic; Methods; Military Personnel; Monitor; Muscle; 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; specific biomarkers; treadmill; white matter; white matter injury

 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(由申请者提供)：每年有数百万美国人因体育相关事件、事故或服兵役而脑震荡。虽然已经进行了广泛的研究来确定诊断脑震荡的生物标记物，但还没有确定脑震荡恢复的特定生物标记物。脑震荡是一种对脑血流(CBF)和自主神经系统(ANS)功能有生理影响的脑损伤。这些影响可能就是为什么运动会加剧脑震荡症状的原因。因此，运动不耐受是脑震荡的一种生理迹象。因此，正常的运动耐量意味着生理恢复。我们的长期目标是更好地了解脑震荡的全身生理障碍，开发可靠的方法来鉴别脑震荡和脑震荡后综合征，建立客观的康复标志，并开发新的治疗方法来加速康复。这项应用的总体目标是确定脑震荡中运动耐受的生理机制。提出这项研究的理由是，我们的工作可能表明，系统地确定运动耐量的恢复是脑震荡恢复的特定生物学标志。这将帮助患者和临床医生自信地知道何时恢复活动是安全的。我们开发了水牛震荡跑步机测试，以系统地评估脑震荡运动员的运动耐量。我们发现，脑震荡后运动时脑血流量异常升高，与对二氧化碳影响钝化呼吸的敏感性改变有关。我们还检测到脑震荡后心输出量(CO)降低。一个根本的问题是，脑震荡后的运动耐力是中枢受限(大脑)还是外围受限(心血管/肌肉)。我们将通过追求以下两个具体目标来研究这一点：(1)确定脑震荡运动耐受性的来源(中枢或外周)和(2)确定脑震荡中枢性运动耐受性的机制。脑震荡的男性和女性参与者在脑震荡后不久和康复后不久的水牛城跑步机运动测试中，将测量脑震荡后不久和康复时的二氧化碳敏感性、通气量、脑血流量(通过MRI中的动脉自旋标记)、血乳酸和CO，以及在核磁共振机器中的模拟运动(头低位倾斜，HDT)。我们还将测量弥散张量成像以评估脑干和穹窿体部的损伤。这些数值将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耐量异常的生理机制是CBF异常控制的核心。这项工作有望确定正常生理(和正常运动耐量)的恢复是脑震荡恢复的一个功能生物标记物。这项工作意义重大，因为生理生物标记物将影响临床判断患者如何从脑震荡中恢复，即从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耐量作为脑震荡导致的脑血流异常生理控制的临床测量。