Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players

Sandy R Shultz; Caroline J Taylor; Riemke Aggio-Bruce; William T O'Brien; Mujun Sun; Adrian V Cioanca; George Neocleous; Georgia F Symons; Rhys D Brady; Anandwardhan A Hardikar; Mugdha V Joglekar; Daniel M Costello; Terence J O'Brien; Riccardo Natoli; Stuart J McDonald

doi:10.1177/11772719221081318

Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players

Biomark Insights. 2022 Feb 28:17:11772719221081318. doi: 10.1177/11772719221081318. eCollection 2022.

Authors

Sandy R Shultz^{1

2}, Caroline J Taylor³, Riemke Aggio-Bruce^{4

5}, William T O'Brien¹, Mujun Sun¹, Adrian V Cioanca⁴, George Neocleous³, Georgia F Symons¹, Rhys D Brady¹, Anandwardhan A Hardikar⁶, Mugdha V Joglekar⁶, Daniel M Costello², Terence J O'Brien^{1

4}, Riccardo Natoli^{4

5}, Stuart J McDonald^{1

3}

Affiliations

¹ Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
² Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.
³ Department of Physiology, Anatomy, and Microbiology, La Trobe University, Melbourne, VIC, Australia.
⁴ The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
⁵ ANU Medical School, The Australian National University, Canberra, ACT, Australia.
⁶ School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.

Abstract

Introduction: Sports-related concussion (SRC) is a common form of brain injury that lacks reliable methods to guide clinical decisions. MicroRNAs (miRNAs) can influence biological processes involved in SRC, and measurement of miRNAs in biological fluids may provide objective diagnostic and return to play/recovery biomarkers. Therefore, this prospective study investigated the temporal profile of circulating miRNA levels in concussed male and female athletes.

Methods: Pre-season baseline blood samples were collected from amateur Australian rules football players (82 males, 45 females). Of these, 20 males and 8 females sustained an SRC during the subsequent season and underwent blood sampling at 2-, 6- and 13-days post-injury. A miRNA discovery Open Array was conducted on plasma to assess the expression of 754 known/validated miRNAs. miRNA target identified were further investigated with quantitative real-time PCR (qRT-PCR) in a validation study. Data pertaining to SRC symptoms, demographics, sporting history, education history and concussion history were also collected.

Results: Discovery analysis identified 18 candidate miRNA. The consequent validation study found that plasma miR-221-3p levels were decreased at 6d and 13d, and that miR-27a-3p levels were decreased at 6d, when compared to baseline. Moreover, miR-27a and miR-221-3p levels were inversely correlated with SRC symptom severity.

Conclusion: Circulating levels of miR-27a-3p and miR-221-3p were decreased in the sub-acute stages after SRC, and were inversely correlated with SRC symptom severity. Although further studies are required, these analyses have identified miRNA biomarker candidates of SRC severity and recovery that may one day assist in its clinical management.

Keywords: Traumatic brain injury; biomarker; inflammation; mild traumatic brain injury; pathophysiology; vascular injury.