• Alex P Di Battista, Nathan Churchill, Tom A Schweizer, Shawn G Rhind, Doug Richards, Andrew J Baker, and Michael G Hutchison.
• Faculty of Kinesiology & Physical Education, University of Toronto, Toronto, ON, Canada; Defence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada. Electronic address: alex.dibattista@utoronto.ca.
• J. Neuroimmunol. 2018 Jun 15; 319: 1-8.

BackgroundSecondary injury pathophysiology after sport-related concussion (SRC) is poorly understood. Blood biomarkers may be a useful tool for characterizing these processes, yet there are limitations in their application as a single modality. Combining blood biomarker analysis with advanced neuroimaging may help validate their continued utility in brain injury research by elucidating important secondary injury mechanisms. Hence, the purpose of this study was to evaluate co-modulation between peripheral blood biomarkers and advanced functional brain imaging after SRC.MethodsForty-three university level athletes from 7 sports were recruited (16 recently concussed athletes; 15 healthy athletes with no prior history of concussion; 12 healthy athletes with a history of concussion). Seven blood biomarkers were evaluated: s100B, total tau (T-tau), von Willebrand factor (vWF), brain derived neurotrophic factor (BDNF), peroxiredoxin (PRDX)-6, monocyte chemoattractant protein (MCP)-1 and -4. Resting-state functional MRI was employed to assess global neural connectivity (Gconn), and arterial spin labelling was used to evaluate cerebral blood flow (CBF). We tested for concurrent alterations in blood biomarkers and MRI measures of brain function between athlete groups using a non-parametric, bootstrapped resampling framework.ResultsCompared to healthy athletes, recently concussed athletes showed greater concurrent alterations in several peripheral blood biomarker and MRI measures: a decrease in T-Tau and Gconn, a decrease in T-Tau and CBF, a decrease in Gconn with elevated PRDX-6, a decrease in CBF with elevated PRDX-6, and a decrease in Gconn with elevated MCP-4. In addition, compared to healthy athletes with no concussion history, healthy athletes with a history of concussion displayed greater concurrent alterations in blood biomarkers and Gconn; lower GConn covaried with higher blood levels of s100B and MCP-4.ConclusionWe identified robust relationships between peripheral blood biomarkers and MRI measures in both recently concussed athletes and healthy athletes with a history of concussion. The results from this combinatorial approach further support that human concussion is associated with inflammation, oxidative stress, and cellular damage, and that physiological perturbations may extend chronically beyond recovery. Finally, our results support the continued implementation of blood biomarkers as a tool to investigate brain injury, particularly in a multimodal framework.Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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