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

Abstract

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. Abstract 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 (CVRCO2hyper${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$/CVRCO2hypo${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$) 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.

Unlocking the complications of chronic concussion in rugby players: A traumatic tale of cerebral injury

“…As would be expected with chronic exposure to contact events, Owens et al. ( 2023 ) found that the players with a previous history of at least one concussion had persistent neurological symptoms. These symptoms included headache, worsened memory, and feelings of anxiety.…”

“…Overall, the authors found that retired rugby union players with a history of concussion were defined by the presence of lower systemic bioactive NO and persistent neurological symptoms, which were accompanied by cognitive impairment and cerebrovascular dysfunction at rest and in response to hyper-/hypocapnia. The current findings by Owens et al (2023) naturally lead to questions related to the impacts of acute concussion on this biomolecular-cerebrovascular-neurocognitive cascade and where interventions may occur to help improve long-term care in athletes exposed to repetitive contact activities. Indeed, data suggest that in the 7 days following a concussion in young athletes, dynamic changes in cerebral blood flow and microstructure seem to occur, though with a large degree of heterogeneity (Churchill et al, 2017).…”

“…In the current issue of Experimental Physiology, Owens et al (2023) present data from a cohesive study aimed at assessing the connections between biomolecular, cerebrovascular and neurocognitive outcomes in retired rugby union players with an established medical history of concussion. This study hypothesized that these players with a history of concussion, compared to otherwise healthy controls, would As would be expected with chronic exposure to contact events, Owens et al (2023) found that the players with a previous history of at least one concussion had persistent neurological symptoms.…”

“…Accordingly, the repeated subconcussive and concussive head impacts/injuries experienced in contact sports may progressively alter cerebrovascular function and structure. The work presented by Owens et al (2023) may also have a broader impact as annual traumatic brain injury (TBI)-related emergency department visits number in the millions, with many TBI-related hospitalizations and deaths in the general population (Capizzi et al, 2020). Therefore, understanding the underlying physiological mechanisms and the overall detrimental effect of repeated subconcussive head impacts or concussions are crucial for the proper acute and chronic treatment of concussion for improved long-term outcomes in both athletes and non-athletes.…”

“…Therefore, Owens et al. ( 2023 ) studied retired rugby union players and matched controls during two visits. Visit 1 included a medical exam, dietary intake assessments and an exercise stress test.…”