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We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS preventing sports participation as well as limiting work, school and\/or social activities for\u2009\u2265\u20096\u00a0months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Following a spinal tap, we analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age- and sex-matched controls exercising\u2009\u2264\u20092 times\/week at low-to-moderate intensity. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17\u00a0months prior to the investigation. CSF cytokines and chemokines levels were significantly increased in eight (IL-2, TNF-\u03b1, IL-15, TNF-\u03b2, VEGF, Eotaxin, IP-10, and TARC), significantly decreased in one (Eotaxin-3), and unaltered in 16 in SRC athletes when compared to controls, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (\n                    <jats:italic>Z<\/jats:italic>\n                    \u2009&lt;\u2009\u2212\u00a01.5) on cognitive testing. Individual biomarker concentrations did not strongly correlate with symptom rating or cognitive function. Limitations include evaluation at a single post-injury time point in relatively small cohorts, and no control group of concussed athletes without persisting symptoms was included. Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.\n                  <\/jats:p>","DOI":"10.1186\/s12974-023-02864-0","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T04:02:39Z","timestamp":1692244959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cerebrospinal fluid levels of neuroinflammatory biomarkers are increased in athletes with persistent post-concussive symptoms following sports-related concussion"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-5324","authenticated-orcid":false,"given":"Anna","family":"Gard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Vedung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Piehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Khademi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Portonova","family":"Wernersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ia","family":"Rorsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3628-0705","authenticated-orcid":false,"given":"Yelverton","family":"Tegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Pessah-Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Ruscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-5626","authenticated-orcid":false,"given":"Niklas","family":"Marklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"2864_CR1","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1136\/bjsports-2016-097393","volume":"51","author":"P McCrory","year":"2017","unstructured":"McCrory P, Feddermann-Demont N, Dvorak J, et al. 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All participants received oral and written information, and signed a written consent form prior to participation. The study was approved by the Regional Ethics Committee of Lund University, Lund, Sweden (Dnr 2017\/1049), the Regional Ethical Review Board in Stockholm, Sweden (Dnr 2014\/1201-31\/1), and the Regional Research Ethics Committee in Uppsala, Sweden (Dnr 2015\/012).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"NM and YT are scientific advisors for PolarCool<sup>\u00a9<\/sup> Inc., dealing with head\u2013neck cooling in the acute management of sports concussion, of no relevance to the present study. No other author declare a competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"189"}}