Serum Protein Biomarker Findings Reflective of Oxidative Stress and Vascular Abnormalities in Male, but Not Female, Collision Sport Athletes.

Brendan P Major,Roxanne Aniceto,Sandy R Shultz,William T O'Brien,I-Hsuan Lin,Terence J O'Brien,Stuart J Mcdonald,Jesse Mccullough,Georgia F Symons,Meng Law,Mujun Sun,Richelle Mychasiuk,Rhys D Brady,Meaghan Clough,Denes V Agoston,Daniel Costello

doi:10.3389/fneur.2020.549624

Abstract

Studies have indicated that concussive and sub-concussive brain injuries that are frequent during collision sports may lead to long-term neurological abnormalities, however there is a knowledge gap on how biological sex modifies outcomes. Blood-based biomarkers can help to identify the molecular pathology induced by brain injuries and to better understand how biological sex affects the molecular changes. We therefore analyzed serum protein biomarkers in male (n = 50) and female (n = 33) amateur Australian rules footballers (i.e., Australia's most participated collision sport), both with a history of concussion (HoC) and without a history of concussion (NoHoC). These profiles were compared to those of age-matched control male (n = 24) and female (n = 20) athletes with no history of neurotrauma or participation in collision sports. Serum levels of protein markers indicative of neuronal, axonal and glial injury (UCH-L1, NfL, tau, p-tau, GFAP, BLBP, PEA15), metabolic (4-HNE) and vascular changes (VEGF-A, vWF, CLDN5), and inflammation (HMGB1) were assessed using reverse phase protein microarrays. Male, but not female, footballers had increased serum levels of VEGF-A compared to controls regardless of concussion history. In addition, only male footballers who had HoC had increased serum levels of 4-HNE. These findings being restricted to males may be related to shorter collision sport career lengths for females compared to males. In summary, these findings show that male Australian rules footballers have elevated levels of serum biomarkers indicative of vascular abnormalities (VEGF-A) and oxidative stress (4-HNE) in comparison to non-collision control athletes. While future studies are required to determine how these findings relate to neurological function, serum levels of VEGF-A and 4-HNE may be useful to monitor subclinical neurological injury in males participating in collision sports.

Highlights

There is growing evidence that exposure to repetitive head impacts (RHI) during participation in collision sports are associated with short- and long-term neurological abnormalities [1,2,3]
To provide additional insight into the pathophysiological consequences of RHI exposure, and examine how biological sex may modify this response, this study examined the effect of playing collision sports on the serum levels of protein biomarkers indicative of neuronal, axonal, glial and vascular injuries, inflammation, and oxidative stress in male and female amateur Australian rules footballers both with a history of concussion (HoC) and without a history of concussion (NoHoC)
This study investigated serum levels of protein biomarkers indicative of neuronal, astroglia, axonal and vascular injury, oxidative stress, and inflammation in male and female Australian rules footballers both with and without a HoC, as well as a control group of non-collision sport athletes with no history of neurotrauma

Summary

Introduction

There is growing evidence that exposure to repetitive head impacts (RHI) during participation in collision sports are associated with short- and long-term neurological abnormalities [1,2,3]. The majority of blood biomarker studies have focused on the acute aftermath of concussion, there is initial evidence that there are chronic systemic changes in athletes with a history of RHI exposure. None of the athletes in this study had reported a concussion within a year prior to the testing and the affected markers were different between male and female athletes. These early findings suggest that RHI exposure in collision sports may trigger a lasting inflammatory response, and that the response is affected by the biological sex

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Results

Conclusion