{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:19:19Z","timestamp":1790813959538,"version":"4.1.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathophysiology and outcomes after traumatic brain injury (TBI) are complex and heterogeneous. Current classifications are uninformative about pathophysiology. Proteomic approaches with fluid-based biomarkers are ideal for exploring complex disease mechanisms, because they enable sensitive assessment of an expansive range of processes potentially relevant to TBI pathophysiology. We used novel high-dimensional, multiplex proteomic assays to assess altered plasma protein expression in acute TBI.<\/jats:p>\n                  <jats:p>We analysed samples from 88 participants from the BIO-AX-TBI cohort [n = 38 moderate\u2013severe TBI (Mayo Criteria), n = 22 non-TBI trauma and n = 28 non-injured controls] on two platforms: Alamar NULISA\u2122 CNS Diseases and OLINK\u00ae Target 96 Inflammation. Patient participants were enrolled after hospital admission, and samples were taken at a single time point \u226410 days post-injury. Participants also had neurofilament light, GFAP, total tau, UCH-L1 (all Simoa\u00ae) and S100B (Millipore) data. The Alamar panel assesses 120 proteins, most of which were previously unexplored in TBI, plus proteins with known TBI specificity, such as GFAP. A subset (n = 29 TBI and n = 24 non-injured controls) also had subacute (10 days to 6 weeks post-injury) 3\u2005T MRI measures of lesion volume and white matter injury (fractional anisotropy).<\/jats:p>\n                  <jats:p>Differential expression analysis identified 16 proteins with TBI-specific significantly different plasma expression. These were neuronal markers (calbindin 2, UCH-L1 and visinin-like protein 1), astroglial markers (S100B and GFAP), neurodegenerative disease proteins (total tau, pTau231, PSEN1, amyloid-beta-42 and 14-3-3\u03b3), inflammatory cytokines (IL16, CCL2 and ficolin 2) and cell signalling- (SFRP1), cell metabolism- (MDH1) and autophagy-related (sequestome 1) proteins. Acute plasma levels of UCH-L1, PSEN1, total tau and pTau231 were correlated with subacute lesion volume. Sequestome 1 was positively correlated with white matter fractional anisotropy, whereas CCL2 was inversely correlated. Neuronal, astroglial, tau and neurodegenerative proteins were correlated with each other, IL16, MDH1 and sequestome 1. Exploratory clustering (k means) by acute protein expression identified three TBI subgroups that differed in injury patterns, but not in age or outcome. One TBI cluster had significantly lower white matter fractional anisotropy than control-predominant clusters but had significantly lower lesion subacute lesion volumes than another TBI cluster. Proteins that overlapped on two platforms had excellent (r &amp;gt; 0.8) correlations between values.<\/jats:p>\n                  <jats:p>We identified TBI-specific changes in acute plasma levels of proteins involved in neurodegenerative disease, inflammatory and cellular processes. These changes were related to patterns of injury, thus demonstrating that processes previously studied only in animal models are also relevant in human TBI pathophysiology. Our study highlights how proteomic approaches might improve classification and understanding of TBI pathophysiology, with implications for prognostication and treatment development.<\/jats:p>","DOI":"10.1093\/brain\/awae305","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T15:25:36Z","timestamp":1727191536000},"page":"1015-1030","source":"Crossref","is-referenced-by-count":28,"title":["High-dimensional proteomic analysis for pathophysiological classification of traumatic brain injury"],"prefix":"10.1093","volume":"148","author":[{"given":"Lucia M","family":"Li","sequence":"first","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , London W12 0BZ ,","place":["UK"]},{"name":"UK Dementia Research Institute Centre for Care Research & Technology , Imperial College London and University of Surrey, London W12 0BZ 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and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , Gothenburg 431 41 ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal 413 45 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-3368","authenticated-orcid":false,"given":"Neil","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , London W12 0BZ ,","place":["UK"]},{"name":"UK Dementia Research Institute Centre for Care Research & Technology , Imperial College London and University of Surrey, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , London W12 0BZ ,","place":["UK"]},{"name":"UK Dementia Research Institute Centre for Care Research & Technology , Imperial College London and University of Surrey, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Soreq","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , London W12 0BZ ,","place":["UK"]},{"name":"UK Dementia Research Institute Centre for Care Research & Technology , Imperial College London and University of Surrey, London W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-4220","authenticated-orcid":false,"given":"Thomas","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , London W12 0BZ ,","place":["UK"]},{"name":"UK Dementia Research Institute Centre for Care Research & Technology , Imperial College London and University of Surrey, London W12 0BZ 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