Sympathetic Activation and Cerebrovascular Pressure Reactivity after Traumatic Brain Injury (TBI)

创伤性脑损伤 (TBI) 后的交感神经激活和脑血管压力反应性

• 批准号: 10714590
• 负责人: Gilberto Moralez
• 金额: $ 40.72万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714590
• 关键词: Acute; Adult; Age; Amnesia; Attenuated; Autonomic Dysfunction; Autonomic nervous system; Blood Pressure; Blood Pressure Monitors; Brain; Cerebrovascular Circulation; Chronic Phase; Clinical; Cognition; Cognitive; Data; Enrollment; Equilibrium; Frequencies; Functional disorder; Future; Glasgow Coma Scale; Glasgow Outcome Scale; Goals; Heart Diseases; Heart Rate; Hospital Mortality; Hour; Impairment; Individual; Injury; Inpatients; Intracranial Pressure; Knowledge; Measurement; Measures; Mediating; Mission; Monitor; Muscle; National Institute of Neurological Disorders and Stroke; Nerve; Nervous System; Nervous System Physiology; Nervous System control; Outcome; Parasympathetic Nervous System; Patient Admission; Persons; Play; Process; Prognostic Marker; Public Health; Recording of previous events; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Sympathetic Nervous System; Telephone; Temperature; Testing; Time; Transcranial Doppler Ultrasonography; Traumatic Brain Injury; Treatment Protocols; Unconscious State; cerebrovascular; cognitive disability; cognitive recovery; cohort; follow-up; functional outcomes; heart rate variability; indexing; innovation; mortality risk; nervous system disorder; physically handicapped; pressure; prevent; prognostication; sex; vasoconstriction

PROJECT SUMMARY/ABSTRACT Moderate to severe traumatic brain injury (TBI) is associated with acute impairments in cerebrovascular pressure reactivity (CVPR); however, the course of recovery and implications for neurorecovery and functional outcome with persistently impaired CVPR after the acute injury are unknown. To date, research into CVPR impairments have focused on the pressure reactivity index (PRx), which requires invasive intracranial pressure (ICP) and arterial blood pressure monitoring. Transcranial Doppler ultrasound (TCD) has the potential to non- invasively measure the pressure reactivity index (nPRx), allowing for assessment of CVPR outside the ICU. Alterations in autonomic nervous system (ANS) function may contribute to CVPR abnormalities after moderate to severe TBI. Cerebrovascular blood flow (CBF) is partially regulated through the balance of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity. Clinical signs of SNS overactivity are seen acutely after TBI, but long-term assessments with objective measures of SNS activity are lacking. The long-term goal is to understand how persistent CVPR impairments impact long-term outcomes after moderate to severe TBI, which is necessary for better prognostication and treatment protocols. At the present time, no known treatments exist to prevent or attenuate the devastating effects of TBI, in part due to the poor understanding of underlying pathophysiologic processes. The following specific aims will be studied to achieve the overall objective: 1) Quantify the trajectories of impaired CVPR over the first year after moderate to severe TBI; 2) Characterize the extent to which ANS dysfunction persists in the first year after moderate to severe TBI; 3) Determine the extent to which impaired CVPR is correlated with ANS dysfunction after moderate to severe TBI; and 4) Explore the extent to which impaired CVPR and ANS dysfunction is associated with functional outcomes 12 months following moderate to severe TBI. A longitudinal assessment of CVPR and ANS function over the first 12 months following injury will be conducted in a cohort of 95 individuals with moderate to severe TBI (Glasgow Coma Scale [GCS] 3-12, loss of consciousness [LOC] greater than 30 minutes, or post- traumatic amnesia [PTA] greater than 1 hour). An additionally cohort of 95 age- and sex-matched healthy controls without prior history of TBI or cardiac disease will be enrolled for comparison. The non-invasive pressure reactivity index (nPRx) will be used as a measure of CVPR, MSNA will be used to objectively measure SNS activity, and HRV will be used to evaluate PNS activity at baseline (prior to inpatient rehabilitation discharge) and quarterly intervals for 12 months following rehabilitation discharge. Individuals with moderate to severe TBI will be assessed for overall functional outcomes using the Glasgow Outcome Scale-Extended (GOS-E) and cognitive status using the Brief Test of Adult Cognition by Telephone (BTACT) at 12-month follow-up. The proposed project is innovative because it will be the first to assess objective measures of CVPR and ANS dysfunction longitudinally for 12 months following moderate to severe TBI.

项目摘要/摘要 中度至重度脑损伤（TBI）与脑血管中的急性障碍有关 压力反应性（CVPR）；但是，恢复的过程以及对神经新闻和功能的影响 急性损伤后CVPR持续受损的结果尚不清楚。迄今为止，研究CVPR 损伤集中在压力反应性指数（PRX）上，这需要侵入性颅内压 （ICP）和动脉血压监测。经颅多普勒超声（TCD）具有非 - 侵入性测量压力反应性指数（NPRX），允许评估ICU之外的CVPR。 自主神经系统（ANS）功能的改变可能会导致中度的CVPR异常 严重的TBI。脑血管血流（CBF）通过交感神经的平衡部分调节 神经系统（SNS）和副交感神经系统（PNS）活性。 SNS过度活动的临床体征 在TBI之后敏锐地看到，但是缺乏具有SNS活动的客观度量的长期评估。 长期目标是了解持续的CVPR损害如何影响长期结果 中度至重度TBI，这对于更好的预后和治疗方案是必不可少的。目前 时间，没有已知的治疗方法可以预防或衰减TBI的破坏性影响，部分原因是 了解潜在的病理生理过程。将研究以下特定目标以实现 总体目标：1）量化中度至重度后的第一年中CVPR受损的轨迹 tbi; 2）表征中度至重度TBI后第一年的ANS功能障碍持续的程度； 3）确定中度至重度后，CVPR受损的程度与ANS功能障碍相关 tbi; 4）探索CVPR和ANS功能障碍与功能相关的程度 中度至重度TBI后12个月的结局。 CVPR和ANS功能的纵向评估 在受伤后的前12个月中，将在95个中度至重度的人群中进行 TBI（格拉斯哥昏迷量表[GCS] 3-12，意识的丧失[LOC]超过30分钟或之后 创伤性健忘症[PTA]大于1小时）。另外还有95岁和性别匹配的健康 没有先前的TBI或心脏病病史的对照进行比较。无创的 压力反应性指数（NPRX）将用作CVPR的量度，MSNA将用于客观性 测量SNS活性，HRV将用于评估基线时的PNS活动（在住院之前 康复恢复）和季度间隔恢复出院后12个月。个人 使用格拉斯哥结果，将评估中度至重度TBI的整体功能结果 使用电话（BTACT）简要测试成人认知（BTACT） 12个月的随访。拟议的项目具有创新性，因为它将是第一个评估目标的项目 中度至重度TBI后，CVPR和ANS功能障碍纵向12个月。