{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:31Z","timestamp":1787028571824,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministry of Health","doi-asserted-by":"publisher","award":["RC2025-2027"],"award-info":[{"award-number":["RC2025-2027"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI), a leading cause of mortality and disability, recognizes a primary, immediate injury due to external forces, and a secondary phase that includes inflammation that can lead to complications such as the post-traumatic confusional state (PTCS), potentially impacting long-term neurological recovery. An earlier identification of these complications, including PTCS, upon admission to intensive rehabilitation units (IRU) could possibly allow the design of personalized rehabilitation protocols in the immediate post-acute phase of moderate-to-severe TBI. The present study aims to identify potential biomarkers to distinguish between TBI patients with and without PTCS. We analyzed cellular and molecular mechanisms involved in neuroinflammation (IL-6, IL-1\u03b2, IL-10 cytokines), neuroendocrine function (norepinephrine, NE, epinephrine, E, dopamine), and neurogenesis (glial cell line-derived neurotrophic factor, GDNF, insuline-like growth factor 1, IGF-1, nerve growth factor, NGF, brain-derived growth factor, BDNF) using enzyme-linked immunosorbent assay (ELISA), comparing results between 29 TBI patients (17 with PTCS and 12 non-confused) and 34 healthy controls (HC), and correlating results with an actigraphy-derived sleep efficiency parameter. In TBI patients compared to HC, serum concentration of (1) pro-inflammatory IL-1\u03b2 cytokine was significantly increased while that of anti-inflammatory IL-10 cytokine was significantly decreased; (2) NE, E and DA were significantly increased; (3) GDNF, NGF and IGF-1 were significantly increased while that of BDNF was significantly decreased. Importantly, IL-10 serum concentration was significantly lower in PTCS than in non-confused patients, correlating positively with an improved actigraphy-derived sleep efficiency parameter. An anti-inflammatory environment may be associated with better prognosis after TBI.<\/jats:p>","DOI":"10.3390\/ijms26178593","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T09:18:57Z","timestamp":1756977537000},"page":"8593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuroinflammatory Signature of Post-Traumatic Confusional State: The Role of Cytokines in Moderate-to-Severe Traumatic Brain Injury"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-1169","authenticated-orcid":false,"given":"Federica","family":"Piancone","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-9505","authenticated-orcid":false,"given":"Francesca","family":"La Rosa","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-6452","authenticated-orcid":false,"given":"Ambra","family":"Hernis","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Marventano","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-6825","authenticated-orcid":false,"given":"Pietro","family":"Arcuri","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1638-7978","authenticated-orcid":false,"given":"Marco","family":"Rabuffetti","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Navarro","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-3043","authenticated-orcid":false,"given":"Marina","family":"Saresella","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-6191","authenticated-orcid":false,"given":"Mario","family":"Clerici","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-019X","authenticated-orcid":false,"given":"Angela","family":"Comanducci","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.apmr.2020.06.021","article-title":"Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria","volume":"101","author":"Sherer","year":"2020","journal-title":"Arch. 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