Decreased Microvascular Cerebral Blood Flow Assessed by Diffuse Correlation Spectroscopy after Repetitive Concussions in Mice

Repetitive concussions are associated with long-term cognitive dysfunction that can be attenuated by increasing the time intervals between concussions; however, biomarkers of the safest rest interval between injuries remain undefined. We hypothesize that deranged cerebral blood flow (CBF) is a candidate biomarker for vulnerability to repetitive concussions. Using a mouse model of human concussion, we examined the effect of single and repetitive concussions on cognition and on an index of CBF (CBF i ) measured with diffuse correlation spectroscopy. After a single mild concussion, CBF i was reduced by 35±4% at 4 hours ( P < 0.01 versus baseline) and returned to preinjury levels by 24 hours. After five concussions spaced 1 day apart, CBF i was also reduced from preinjury levels 4 hours after each concussion but had returned to preinjury levels by 72 hours after the final concussion. Interestingly, in this repetitive concussion model, lower CBF i values measured both preinjury and 4 hours after the third concussion were associated with worse performance on the Morris water maze assessed 72 hours after the final concussion. We conclude that low CBF i measured either before or early on in the evolution of injury caused by repetitive concussions could be a useful predictor of cognitive outcome.