Cerebrovascular Neuroprotection after Acute Concussion in Adolescents

Abstract

Objective: To assess acute cerebrovascular function in concussed adolescents (14-21 years of age), whether it is related to resting cerebral hemodynamics, and whether it recovers chronically. Methods: Cerebral vasoreactivity and autoregulation, based on middle cerebral artery blood flow velocity, was assessed in 28 concussed participants (≤14 days of injury) and 29 matched controls. The participants in the concussion group returned for an 8-week follow-up assessment. Over the course of those 8-weeks, participants recorded aerobic exercise frequency and duration. Results: Between groups, demographic, clinical, and hemodynamic variables were not significantly different. Vasoreactivity was significantly higher in the concussed group (p = 0.02). Within the concussed group, 60% of the variability in resting cerebral blood flow velocity was explained by vasoreactivity and two components of autoregulationfalling slope and effectiveness of autoregulation (adjusted R 2 = 0.60, p < 0.001). Moreover, lower mean arterial pressure, lower responses to increases in arterial pressure, and lower vasoreactivity were significantly associated with larger symptom burden (adjusted R 2 = 0.72, p < 0.01). By the 8-week timepoint, symptom burden, but not vasoreactivity, improved in all but four concussed participants (p < 0.01). 8-week change in vasoreactivity was positively associated with aerobic exercise volume (adjusted R 2 = 0.19, p = 0.02). Interpretation: Concussion resulted in changes in cerebrovascular regulatory mechanisms, which in turn explained the variability in resting cerebral blood flow velocity and acute symptom burden. Furthermore, these alterations persisted chronically despite symptom resolution, but was positively modified by aerobic exercise volume. These findings provide a mechanistic framework for further investigation into underlying cerebrovascular related symptomatology.

Association of Hemodynamic and Cerebrovascular Responses to Exercise With Symptom Severity in Adolescents and Young Adults With Concussion

“…36 Collectively, these results suggest that high sensitivity of cerebral vasculature to arterial CO 2 may, at least partly, underlie concussion symptoms. Past work from our group indicates the degree of vascular sensitivity to arterial CO 2 (i.e., cerebral vasoactivity) positively relates to the level of concussion symptoms both acutely 14 and chronically 15 after injury. Thus, based on prior data at rest, it stands to reason that high sensitivity to arterial CO 2 results in quick increase in CBF beyond what is needed by neural activity, leading to symptom exacerbation.…”

“…11 Consequently, during a bout of progressive exercise, arterial CO 2 initially increases, followed by a reduction. 12,13 Our prior work suggested that resting cerebrovascular sensitivity to arterial CO 2 (cerebral vasoactivity) is higher among those who experienced a concussion compared with healthy controls, to a level that is proportional to symptom burden at rest acutely 14 and chronically. 15 Thus, higher cerebrovascular sensitivity to increases in CO 2 during exercise may lead to an increase in CBF beyond what is needed to meet the metabolic demand, and this may underlie exercise-related symptom exacerbation.…”

“…Cerebral vasoactivity was quantified using a piecewise linear regression to determine the linear portion of the relationship between cerebrovascular conductance and end-tidal CO 2 . 14,19 We used ETCO 2 to ensure comparability of our results vis-a-vis vasoactivity to previous ones. The slope of this relationship was used as a measure of cerebral vasoactivity as is standard for this methodology.…”

Postconcussion Dizziness Severity Predicts Daily Step Count during Recovery among Adolescent Athletes

“…One possible contributing factor to dizziness after concussion is cerebrovascular dysfunction, specifically impaired cerebrovascular autoregulation, leading to decreased blood flow to the brain (36). Impaired cerebrovascular regulation has been observed within 2 wk of concussion and relates to symptom burden in the subacute concussion phase (37). A gradual reintroduction of exercise may help regulate cerebral blood flow, as researchers observed an association between greater physical activity volume and more improvement in cerebrovascular function during concussion recovery (37).…”

“…Impaired cerebrovascular regulation has been observed within 2 wk of concussion and relates to symptom burden in the subacute concussion phase (37). A gradual reintroduction of exercise may help regulate cerebral blood flow, as researchers observed an association between greater physical activity volume and more improvement in cerebrovascular function during concussion recovery (37). The beneficial effect of exercise on cerebrovascular function may also help improve dizziness after concussion (36).…”