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

项目总结/摘要 中重度创伤性脑损伤（TBI）与急性脑血管损伤有关， 压力反应性（CVPR）;然而，恢复过程和对神经恢复和功能的影响 急性损伤后CVPR持续受损的结局尚不清楚。迄今为止，对CVPR的研究 损伤集中在压力反应性指数（PRx），这需要有创颅内压 (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），允许在ICU外评估CVPR。 自主神经系统（ANS）功能的改变可能导致中度CVPR后的CVPR异常 严重的创伤性脑损伤脑血管血流量（CBF）部分通过交感神经系统的平衡调节。 神经系统（SNS）和副交感神经系统（PNS）活动。SNS过度活动的临床体征 在TBI后可以看到严重的SNS活动，但缺乏对SNS活动进行客观测量的长期评估。 长期目标是了解持续性CVPR损伤如何影响治疗后的长期结局。 中度至重度TBI，这对于更好的诊断和治疗方案是必要的。现 目前，还没有已知的治疗方法来预防或减轻TBI的破坏性影响，部分原因是由于TBI的治疗效果差。 了解潜在的病理生理过程。将研究实现以下具体目标 总体目标：1）量化中度至重度CVPR受损后第一年的轨迹 2）表征ANS功能障碍在中度至重度TBI后的第一年中持续的程度; 3)确定CVPR受损与中度至重度治疗后ANS功能障碍的相关程度 TBI;以及4）探索CVPR和ANS功能障碍受损与功能性TBI相关的程度。 中重度TBI后12个月的结果。CVPR和ANS功能的纵向评估 在受伤后的前12个月内，将在95名中度至重度 TBI（格拉斯哥昏迷量表[GCS] 3-12，意识丧失[昏迷]超过30分钟，或 创伤性遗忘（PTA）大于1小时）。另一组95名年龄和性别匹配的健康人， 没有TBI或心脏病既往史的对照组将被招募用于比较。无创 压力反应性指数（nPRx）将被用作CVPR的测量，MSNA将被用于客观地 测量SNS活动，HRV将用于评估基线时（住院治疗前）的PNS活动 康复出院），并在康复出院后每季度进行一次，持续12个月。个人 将使用格拉斯哥结局评估中重度TBI患者的总体功能结局 量表扩展（GOS-E）和使用成人电话认知简易测试（BTACT）的认知状态， 12-月随访。拟议的项目是创新的，因为它将是第一个评估目标 在中度至重度TBI后12个月纵向测量CVPR和ANS功能障碍。

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.