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

项目摘要/摘要 中、重度颅脑损伤与急性脑血管损害相关 压力反应性(CVPR)；然而，恢复过程及其对神经恢复和功能的影响 急性损伤后CVPR持续受损的结果尚不清楚。迄今为止，对CVPR的研究 损伤主要集中在压力反应性指数(PRX)上，这需要侵入性的颅内压。 (颅内压)和动脉血压监测。经颅多普勒超声(TCD)有可能在非 有创性地测量压力反应性指数(NPRx)，以便在ICU外评估CVPR。 中暑后自主神经系统(ANS)功能改变可能与CVPR异常有关 严重的颅脑损伤。脑血管血流量(CBF)的部分调节是通过交感神经平衡来实现的 神经系统(SNS)和副交感神经系统(PNS)活动。社交网络过度活跃的临床征兆 但缺乏对SNS活动进行客观衡量的长期评估。 长期目标是了解持续性的CVPR损伤如何影响术后的长期结果 中度至重度脑外伤，这对于更好的预后和治疗方案是必要的。目前 随着时间的推移，目前还没有已知的治疗方法来预防或减轻脑损伤的破坏性影响，部分原因是穷人 了解潜在的病理生理过程。将研究以下具体目标，以实现 总体目标：1)量化中度至重度CVPR受损的第一年的轨迹 2)表征中重度脑损伤后第一年ANS功能障碍的持续程度； 3)确定中到重度患者CVPR受损与ANS功能障碍的相关程度 以及4)探讨CVPR受损和ANS功能障碍与功能性相关的程度 中至重度颅脑损伤后12个月的结果。CVPR和ANS功能的纵向评估 在受伤后的头12个月内，将对95名中度至重度患者进行队列调查 TBI(格拉斯哥昏迷分级[GCS]3-12，意识丧失[LOC]超过30分钟，或 创伤性健忘症[PTA]超过1小时)。另一组95名年龄和性别匹配的健康人 没有脑损伤或心脏病病史的对照将被纳入进行比较。非侵入性的 压力反应指数(NPRx)将被用来衡量CVPR，MSNA将被用来客观地 测量SNS活动，并使用HRV评估基线(住院患者之前)的PNS活动 康复出院)，康复出院后每季度间隔12个月。个人 对于中度到重度的创伤性脑损伤，将使用格拉斯哥预后评估总体功能预后 扩展版(GOS-E)与成人电话认知简明测验(BTACT)的认知状态 随访12个月。拟议的项目是创新的，因为它将是第一个评估目标的项目 中至重度颅脑损伤后12个月的CVPR和ANS功能障碍的纵向测量。

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.