{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:47:58Z","timestamp":1790185678236,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Fundaci\u00f3n Mutua Madrile\u00f1a and Fondo de Investigaciones Sanitarias (FIS)","doi-asserted-by":"publisher","award":["PI19\/00082"],"award-info":[{"award-number":["PI19\/00082"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Fundaci\u00f3n Mutua Madrile\u00f1a and Fondo de Investigaciones Sanitarias (FIS)","doi-asserted-by":"publisher","award":["PI22\/00362"],"award-info":[{"award-number":["PI22\/00362"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["CNS2023-145023"],"award-info":[{"award-number":["CNS2023-145023"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RED2022-134511-T"],"award-info":[{"award-number":["RED2022-134511-T"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD22\/00101"],"award-info":[{"award-number":["CD22\/00101"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI23\/00135"],"award-info":[{"award-number":["FI23\/00135"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a highly heterogeneous disease and achieving an accurate diagnosis remains a significant challenge. Biomarkers play a crucial role in minimizing the reliance on invasive techniques like computed tomography, which also have significant economic costs. Human samples were obtained from prospective cohort studies. Mice were subjected to an experimental model of traumatic brain injury. Biomarker levels, gene expression, and blood\u2013brain barrier integrity were analyzed using ELISA, qRT-PCR, and Evans Blue assay; data were statistically evaluated using parametric or non-parametric tests as appropriate. This study focuses on evaluating the role of matricellular protein thrombospondin-1 (TSP-1) and the tight junction proteins occludin and ZO-1 as potential biomarkers of TBI. We showed that lower serum TSP-1 levels correlated with poor patient outcomes at 6 months compared to those patients with a good outcome. Additionally, the disruption of the blood\u2013brain barrier (BBB) and subsequent release of tight junction proteins allowed us to identify occludin as a potential biomarker for prognosis in a cohort of TBI patients and as a diagnosis biomarker in a subgroup of patients with mild TBI, but its discriminative power as a diagnosis biomarker appears modest, as reflected by an AUC of 0.693. On the other hand, ZO-1 exhibited increased levels but limited diagnostic utility. These findings highlight the critical role of TSP-1 in maintaining BBB integrity and regulating the inflammatory response after a TBI, supported by the worsened condition observed in TSP-1-deficient animals. These results demonstrate the potential of TSP-1 and occludin as valuable biomarkers for secondary injury and disease progression in patients with mild to moderate\/severe TBI.<\/jats:p>","DOI":"10.3390\/ijms27020571","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the Role of Thrombospodin-1 and Occludin as Potential Prognostic and Diagnostic Biomarkers in Traumatic Brain Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"C\u00e9line","family":"Decouty-P\u00e9rez","sequence":"first","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-8554","authenticated-orcid":false,"given":"In\u00e9s","family":"Valencia","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Alvarez-Rubal","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mart\u00ednez-Cuevas","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-1705","authenticated-orcid":false,"given":"V\u00edctor","family":"Farr\u00e9-Alins","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8615-960X","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Calzada","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Universidad Aut\u00f3noma of Madrid, 28029 Madrid, Spain"},{"name":"Instituto Investigaci\u00f3n Sanitaria-Princesa IIS-IP, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Penalba","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-2279","authenticated-orcid":false,"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Department of Neurology, Hospital Universitario Virgen Macarena, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rodr\u00edguez de C\u00eda","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, Hospital Universitario Santa Cristina, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6234-7662","authenticated-orcid":false,"given":"Mario","family":"Taravilla-Loma","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Hospital Universitario La Paz, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-595X","authenticated-orcid":false,"given":"Borja J.","family":"Hern\u00e1ndez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Hospital Universitario La Paz, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Fuertes-Yebra","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria-Princesa IIS-IP, 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Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:15:30Z","timestamp":1767698130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020571"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020571","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]}}}