{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:22:51Z","timestamp":1791364971524,"version":"4.3.1"},"reference-count":98,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>\n                    The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009192, age 16\u201360 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) &lt;30\u2009min, and post-traumatic amnesia (PTA) &lt;24\u2009h were included. Blood samples were collected at admission (within 72\u2009h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFN\u03b3], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1\u03b2, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72\u2009h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFN\u03b3 were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.\n                  <\/jats:p>","DOI":"10.1089\/neu.2023.0419","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T09:24:35Z","timestamp":1703064275000},"page":"862-878","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury After Mild Traumatic Brain Injury"],"prefix":"10.1177","volume":"41","author":[{"given":"Gerard Janez Brett","family":"Clarke","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."},{"name":"Department of Neuromedicine and Movement Sciences, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toril","family":"Skandsen","sequence":"additional","affiliation":[{"name":"Department of Neuromedicine and Movement Sciences, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."},{"name":"Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden."},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom."},{"name":"UK Dementia Research Institute at UCL, University College London, London, United Kingdom."},{"name":"Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China."},{"name":"Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turid","family":"Follestad","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."},{"name":"Clinical Research Unit Central Norway, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine Elisabeth","family":"Einarsen","sequence":"additional","affiliation":[{"name":"Department of Neuromedicine and Movement Sciences, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."},{"name":"Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Vik","sequence":"additional","affiliation":[{"name":"Department of Neuromedicine and Movement Sciences, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."},{"name":"Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Eirik","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Department of Anesthesiology and Intensive Care Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway."},{"name":"Center of Molecular Inflammation Research, Department of Clinical and Molecular Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren Erik","family":"Pischke","sequence":"additional","affiliation":[{"name":"Department of Immunology, Department of Anesthesiology and Intensive Care Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway."},{"name":"Clinic for Emergencies and Critical Care, Department of Anesthesiology and Intensive Care Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, 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