Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition

Scand J Med Sci Sports. 2021 Dec;31(12):2291-2299. doi: 10.1111/sms.14046. Epub 2021 Sep 12.


Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior-recurrent contact impacts molecular-hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13-19) years playing history reporting 3 (IQR 1-4) concussions. They were compared to 17 sex-age-physical activity-and education-matched non-contact controls with no prior history of self-reported concussion. Venous blood was assayed directly for the ascorbate free radical (A•- electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone-based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia ( CVR CO 2 Hyper / Hypo ). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative-nitrosative stress was confirmed in the players through increased A•- (p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range ( CVR CO 2 Range ; p = 0.045) elevation in neurofilament light-chain (p = 0.010) and frontotemporal impairments in immediate-memory (p = 0.001) delayed-recall (p = 0.048) and fine-motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.

Keywords: cerebral blood flow; cognition; concussion; free radicals; rugby union.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Flow Velocity
  • Brain Concussion / physiopathology*
  • Brain Concussion / psychology*
  • Case-Control Studies
  • Cerebrovascular Circulation*
  • Cognition Disorders / etiology*
  • Football / injuries*
  • Hemodynamics
  • Humans
  • Male
  • Middle Cerebral Artery / physiology
  • Nitric Oxide / blood
  • Oxidative Stress
  • Recurrence
  • Risk Factors


  • Biomarkers
  • Nitric Oxide