{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:34:52Z","timestamp":1790879692791,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016060","name":"Stichting De Cock-Hadders","doi-asserted-by":"publisher","award":["2023\u201072"],"award-info":[{"award-number":["2023\u201072"]}],"id":[{"id":"10.13039\/100016060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up\u2010regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long\u2010term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (&lt;24\u2009h;\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009256) and at 1\u2010month follow\u2010up (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009146). A comparison group of healthy controls (HC;\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200932) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)\u20106 and IL\u201010 were quantified in plasma. Clinical outcome was measured at six months post\u2010injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.57 vs.\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.29) and XA (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.98 vs.\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.32), larger effects sizes were observed during the acute phase compared to one\u2010month follow\u2010up, while for PA (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.49 vs.\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non\u2010significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6\u2009months post\u2010injury. No significant relationships were found for Trp, XA, and PA with IL\u20106 or IL\u201010 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1\u2009month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16137-fig-0005-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16137","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T04:53:24Z","timestamp":1716267204000},"page":"2710-2721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the kynurenine pathway in mild traumatic brain injury: A longitudinal study"],"prefix":"10.1111","volume":"168","author":[{"given":"Koen","family":"Visser","sequence":"first","affiliation":[{"name":"Department of Neurology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ciubotariu","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrthe E.","family":"de Koning","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Spectrum Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van Faassen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"van der Ley","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Mayer","sequence":"additional","affiliation":[{"name":"The Mind Research Network and LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Biomedical Engineering Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno R.","family":"Bourgonje","sequence":"additional","affiliation":[{"name":"The Henry D. Janowitz Division of Gastroenterology, Department of Medicine Icahn School of Medicine at Mount Sinai  New York City New York USA"},{"name":"Department of Gastroenterology and Hepatology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido P.","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"van Goor","sequence":"additional","affiliation":[{"name":"Division of Pathology of the Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joukje","family":"van der Naalt","sequence":"additional","affiliation":[{"name":"Department of 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