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

journal contribution
posted on 25.11.2020, 09:36 by BP Major, Stuart McDonald, WT O'Brien, GF Symons, M Clough, D Costello, M Sun, RD Brady, J Mccullough, R Aniceto, IH Lin, M Law, R Mychasiuk, TJ O'Brien, DV Agoston, SR Shultz
© Copyright © 2020 Major, McDonald, O'Brien, Symons, Clough, Costello, Sun, Brady, Mccullough, Aniceto, Lin, Law, Mychasiuk, O'Brien, Agoston and Shultz. 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.

Funding

This research was funded by grants and fellowships from the National Health and Medical Research Council of Australia to SS.

History

Publication Date

30/09/2020

Journal

Frontiers in Neurology

Volume

11

Article Number

549624

Pagination

10p. (p. 1-10)

Publisher

Frontiers Research Foundation

ISSN

1664-2295

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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