Evidence of a distinct peripheral inflammatory profile in sport-related concussion

Abstract

Background: Inflammation is considered a hallmark of concussion pathophysiology in experimental models, yet is understudied in human injury. Despite the growing use of blood biomarkers in concussion, inflammatory biomarkers have not been well characterized. Furthermore, it is unclear if the systemic inflammatory response to concussion differs from that of musculoskeletal injury. The purpose of this paper was to characterize systemic inflammation after injury in athletes with sport-related concussion or musculoskeletal injury. Methods: A prospective, observational cohort study was conducted employing 175 interuniversity athletes (sport-related concussion, n = 43; musculoskeletal injury, n = 30; healthy, n = 102) from 12 sports at a sports medicine clinic at an academic institution. High-sensitivity immunoassay was used to evaluate 20 inflammatory biomarkers in the peripheral blood of athletes within 7 days of injury (subacute) and at medical clearance. Healthy athletes were sampled prior to the start of their competitive season. Partial least squares regression analyses were used to identify salient biomarker contributions to class separation between injured and healthy athletes, as well as to evaluate the relationship between biomarkers and days to recovery in injured athletes. Results: In the subacute period after injury, compared to healthy athletes, athletes with sport-related concussion had higher levels of the chemokines' monocyte chemoattractant protein-4 (p < 0.001) and macrophage inflammatory protein-1β (p = 0.001); athletes with musculoskeletal injury had higher levels of thymus and activation-regulated chemokine (p = 0.001). No significant differences in biomarker profiles were observed at medical clearance. Furthermore, concentrations of monocyte chemoattractant protein-1 (p = 0.007) and monocyte chemoattractant protein-4 (p < 0.001) at the subacute time point were positively correlated with days to recovery in athletes with sport-related concussion, while thymus and activation-regulated chemokine was (p = 0.001) positively correlated with days to recovery in athletes with musculoskeletal injury. Conclusion: Sport-related concussion is associated with perturbations to systemic inflammatory chemokines that differ from those observed in athletes with a musculoskeletal injury. These results support inflammation as an important facet of secondary injury after sport-related concussion that can be measured systemically in a human model of injury.