{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:19:59Z","timestamp":1780427999168,"version":"3.54.1"},"reference-count":74,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T00:00:00Z","timestamp":1688860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Following retirement from sport, the chronic consequences of prior\u2010recurrent 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\u00a0\u00b1\u00a05\u00a0years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex\u2010, age\u2010, cardiorespiratory fitness\u2010 and education\u2010matched 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\u2010based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light\u2010chain (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 (<jats:italic>U<\/jats:italic>\u00a0=\u00a0109<jats:sub>(41)<\/jats:sub>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.007), with increased severity compared to controls (<jats:italic>U<\/jats:italic>\u00a0=\u00a077<jats:sub>(41)<\/jats:sub>, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Lower total NO bioactivity (<jats:italic>U<\/jats:italic>\u00a0=\u00a0135<jats:sub>(41)<\/jats:sub>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.049) and lower basal MCAv were apparent in players (<jats:italic>F<\/jats:italic><jats:sub>2,39<\/jats:sub>\u00a0=\u00a09.344, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004). This was accompanied by mild cognitive impairment (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.020, 95% CI, \u22123.95 to \u22120.34), including impaired fine\u2010motor coordination (<jats:italic>U<\/jats:italic>\u00a0=\u00a0141<jats:sub>(41)<\/jats:sub>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non\u2010concussed, non\u2010contact controls.<\/jats:p>","DOI":"10.1113\/ep091195","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T01:03:41Z","timestamp":1688951021000},"page":"1029-1046","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players"],"prefix":"10.1113","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-0616","authenticated-orcid":false,"given":"Thomas S.","family":"Owens","sequence":"first","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6757-6448","authenticated-orcid":false,"given":"Christopher J.","family":"Marley","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Calverley","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-7038","authenticated-orcid":false,"given":"Benjamin S.","family":"Stacey","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-0672","authenticated-orcid":false,"given":"Lewis","family":"Fall","sequence":"additional","affiliation":[{"name":"Faculty of Computing, Engineering and Science University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-0497","authenticated-orcid":false,"given":"Hayato","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences Waseda University  Tokorozawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Iannetelli","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Filipponi","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Davies","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Hirtz","sequence":"additional","affiliation":[{"name":"LBPC\u2010PPC University of Montpellier, Institute of Regenerative Medicine\u2010Biotherapy IRMB, Centre Hospitalier Universitaire de Montpellier, INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Lehmann","sequence":"additional","affiliation":[{"name":"LBPC\u2010PPC University of Montpellier, Institute of Regenerative Medicine\u2010Biotherapy IRMB, Centre Hospitalier Universitaire de Montpellier, INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Tuaillon","sequence":"additional","affiliation":[{"name":"CHU Montpellier, Department of Bacteriology\u2010Virology Centre University of  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Marchi","sequence":"additional","affiliation":[{"name":"Cerebrovascular and Glia Research, Department of Neuroscience Institute of Functional Genomics (University of Montpellier, CNRS, INSERM)  Montpellier 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