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

项目总结/文摘

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.