| INTRODUCTION. Traumatic Brain Injury (TBI) is a global health concern. Spanning mild cognitive disturbances to unsurvivable trauma, the clinical challenges of TBI range from acute life-saving predicaments to the management of chronic cognitive impairment. While the primary insult leading to injury is irreversible, the subsequent secondary manifestations are seemingly amenable to intervention. Yet, no effective therapies exist across the spectrum of brain injury, primarily owing to our inability to understand the multifaceted, complex, secondary manifestations that occur after the primary insult. While experimental animal research has been informative in this regard, our knowledge of these processes in humans is lacking. However, a growing body of evidence suggests blood biomarker analysis may be a useful tool to aid in the elucidation of important pathophysiological mechanisms across a range of severities in human TBI. OBJECTIVE. The aim of this thesis was to use blood biomarkers as a tool to advance knowledge of secondary injury processes across the severity spectrum of TBI. METHODS. To investigate moderate-to-severe injury, we evaluated patients over the first 24 h from hospital admission after isolated TBI. To investigate mild injury, we studied varsity athletes with a clinically diagnosed sport-related concussion (SRC), sampled from the subacute period throughout clinical recovery, and chronically up to years after injury. Using multiplex immunoassay techniques, we evaluated a total of 58 blood biomarkers associated with numerous previously defined secondary injury processes, including central nervous system (CNS) injury, sympathetic nervous system (SNS) activity, inflammation, vascular injury and hemostasis. RESULTS. In moderate-to-severe TBI, we found significant, dynamic pathological associations between SNS hyperactivity, inflammation, hemostasis, and vascular injury. In SRC, we found subacute alterations to numerous peripheral indices of CNS injury, inflammation and neuroinjury that persisted at medical clearance, as well as in ostensibly healthy athletes exposed to repetitive head impacts. CONCLUSION. Blood biomarkers are a useful tool to evaluate secondary injury processes across the spectrum of TBI. The results from these works necessitate future investigations into: (1) the potential therapeutic benefit of beta-blockers acutely after moderate-to-severe injury, and (2) the interrelationships between chronic inflammation and CNS injury after SRC, and their potential involvement in neurodegeneration. |
