A prospective, multidisciplinary approach to understanding sport-related head trauma : novel insights into the effects on myelin and cerebrovascular function

Sport-related concussion occurs at an alarmingly high rate, affecting millions each year. Concern is growing over the effects of repetitive subconcussive head trauma towards the development of long-term neurological deficits. There are calls within sports medicine to shift from symptom-based assessments towards reliable, objective tools to improve identification and management of dangerous levels of sport-related head trauma. The overall objective across the five studies of this thesis was to elucidate the roles of brain myelination and cerebrovascular dysfunction within this context. In study 1, myelin water imaging permitted the first direct evaluation of the effect of sport-related head trauma on myelin integrity. While transient post-concussion disruptions in myelin were observed for at least 2-weeks in multiple brain areas, no myelin changes were observed as a consequence of repetitive subconcussive trauma. Study 2 used transcranial Doppler ultrasound to assess the effects of concussion on indices of dynamic cerebral autoregulation (CA), demonstrating a delay in the CA response to blood pressure alterations persisting beyond symptom resolution that is suggestive of autonomic dysregulation of the cerebrovasculature; deficits did not appear to be cumulative across multiple injuries. Study 3 revealed detrimental effects of one season of contact sport participation on both the timing and magnitude of CA responses related to the degree of exposure to repetitive subconcussive head trauma. Study 4 assessed the effect of concussion on neurovascular coupling (NVC) dynamics within the artery supplying the occipital cortex following visual stimulation, and revealed delays in achieving peak response rate in concert with an elevated response magnitude acutely post-injury with resolution by 1-month; deficits did not appear to accumulate across multiple injuries. Study 5 revealed no changes in NVC dynamics as a function of exposure to one season of participation in contact or non-contact sport, suggesting subconcussive trauma may not impair NVC. Collectively, these results suggest sport-related head trauma can impair myelin integrity and cerebrovascular function; the potential role for autonomic dysregulation towards these findings is discussed. While the effect of repetitive subconcussive trauma on susceptibility to injury remains unclear, the disruptions observed following acute concussion highlight the emerging distinction between clinical and physiological recovery.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat