Abstract
Purpose: Blood biomarkers are a useful tool to study concussion. However, their interpretation is complicated by a number of potential biological confounds, including exercise. This is particularly relevant in military and athletic settings where injury commonly occurs during physical exertion. The impact of high-intensity interval training (HIIT) on putative brain injury biomarkers remains under-examined. The purpose of this study was to observe the effects of HIIT on a panel of blood biomarkers associated with brain injury.Methods: Eleven healthy, recreationally active males (median age = 29.0, interquartile range = 26.0–31.5) performed HIIT on a bicycle ergometer (8-12 × 60-s intervals at 100% of peak power output, interspersed by 75-s recovery at 50 W) three times/week for 2 weeks. Peripheral blood samples were collected before and immediately after HIIT during the first and last training sessions. Plasma concentrations of s100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), neurogranin (NRGN), peroxiredoxin (PRDX)-6, creatine kinase-BB isoenzyme (CKBB), visinin-like protein (VILIP)-1, von Willebrand factor (vWF), monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-9, and total tau (T-tau) were quantitated by high-sensitivity MULTI-SPOT® immunoassay, on the MesoScale Diagnostics electrochemiluminescence detection platform. Differences in biomarker concentrations in response to HIIT were evaluated by partial least squares discriminant analysis (PLSDA) within a repeated-measures bootstrapped framework.Results: Ten of 12 biomarkers were increased pre-to-post HIIT; VILIP-1 remained unchanged, and GFAP was not statistically evaluated due to insufficient detectability. After 2 weeks of HIIT, T-tau was no longer significantly elevated pre-to-post HIIT, and significant attenuation was noted in the acute responses of NRGN, PRDX-6, MMP-9, and vWF. In addition, compared to session 1, session 6 pre-exercise concentrations of NSE and VILIP-1 were significantly lower and higher, respectively.Conclusion: Blood biomarkers commonly associated with brain injury are significantly elevated in response to a single bout of HIIT. After a 2-week, six-session training protocol, this response was attenuated for some, but not all markers. While biomarkers continue to provide promise to concussion research, future studies are necessary to disentangle the common biological sequelae to both exercise and brain injury.
Highlights
Blood biomarkers are a promising tool to investigate concussion and other mild forms of brain trauma
As opposed to severe traumatic brain injury (TBI) where peripheral blood biomarker concentrations can acutely fluctuate by several orders of magnitude (Di Battista et al, 2016a), the relatively modest changes observed in concussion are often more difficult to characterize
Volunteers were given a full explanation of the study procedures, including all possible risks and discomforts associated with the study, and provided their written informed consent; the research protocol was approved by the Defence Research and Development Canada Human Research Ethics Committee and University of Toronto Research Ethics Board in accordance with the Declaration of Helsinki
Summary
Blood biomarkers are a promising tool to investigate concussion and other mild forms of brain trauma. Concussions occur frequently in the athletic and military settings where injury commonly accompanies physical exertion (Garber et al, 2014, 2016). This presents both methodological and analytical challenges, as exercise itself elicits profound physiological and biochemical alterations, and many of these perturbations are similar to those seen in concussion and/or mild head trauma (Reihmane et al, 2012; Cook et al, 2013; Koh and Lee, 2014; Stocchero et al, 2014; Bessa et al, 2016; Kaspar et al, 2016; He et al, 2017). The continued use of blood biomarkers for concussion in physically active populations necessitates a better understanding of how they may be affected by both acute and chronic exercise (Broglio et al, 2017)
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