Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players

Thomas S. Owens, Christopher J. Marley, Thomas A. Calverley, Benjamin S. Stacey, Lewis Fall, Hayato Tsukamoto, Angelo Iannetelli, Teresa Filipponi, Bruce Davies, Gareth L. Jones, Christophe Hirtz, Sylvain Lehmann, Edouard Tuaillon, Nicola Marchi, Damian M. Bailey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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New Findings

What is the central question of this study?

What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history?

What is the main finding and its importance?

Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline.

Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia (◂◽.▸/◂◽.▸) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41), P = 0.007), with increased severity compared to controls (U = 77(41), P < 0.001). Lower total NO bioactivity (U = 135(41), P = 0.049) and lower basal MCAv were apparent in players (F2,39 = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, −3.95 to −0.34), including impaired fine-motor coordination (U = 141(41), P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.

Original languageEnglish
Article numberEP091195
Pages (from-to)1029-1046
Number of pages18
JournalExperimental Physiology
Issue number8
Early online date9 Jul 2023
Publication statusPublished - 1 Aug 2023


  • nitric oxide
  • rugby union
  • concussion
  • cerebrovascular function


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