{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:26:16Z","timestamp":1787160376721,"version":"build-2736575974"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric traumatic brain injury (pTBI) often leads to cognitive, behavioral, and motor impairments. NLRP3 inflammasome proteins, such as ASC and caspase-1, may serve as biomarkers for TBI severity due to their role in neuroinflammation. This study aims to assess the association between serum ASC and caspase-1 levels and TBI severity in pediatric patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples were collected at pediatric intensive care unit (ICU) admission (first post-admission), and at 24 and 48\u2009h post-admission, from TBI participants aged 28 days to 18 years and from demographically matched controls. TBI severity was assessed using the Glasgow Coma Scale (GCS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We analyzed samples from 77 pTBI patients and 31 controls. ASC levels were significantly higher across all GCS categories, with the most pronounced differences in the severe category at first post-admission (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005, AUROC 0.83) and 24\u2009h post-admission (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, AUROC 0.83). Caspase-1 levels were significantly elevated in the severe category, particularly at first post-admission (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, AUROC 0.85).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Elevated ASC and caspase-1 levels, especially in severe pTBI cases, suggest their potential as biomarkers for TBI severity. These findings emphasize the role of inflammasome proteins in post-TBI neuroinflammation and support further research into targeted therapies for pediatric TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Increased serum levels of inflammasome proteins ASC and caspase-1 in acute-phase post-admission samples are associated with severe TBI.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>To our knowledge, this is the first study to examine the inflammasome pathway in pediatric TBI patients across the severity spectrum using serum samples.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The study enhances our understanding of NLRP3 inflammasome activation in pediatric TBI by profiling serum levels and examining their clinical correlation with injury severity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It suggests an adjunctive approach to the Glasgow Coma Scale with biomarkers for more precise TBI diagnosis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This research lays the groundwork for future therapeutic strategies targeting inflammasomes in pediatric TBI.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04410-5","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:41:09Z","timestamp":1758890469000},"page":"1494-1503","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of serum inflammasome proteins and pediatric traumatic brain injury severity"],"prefix":"10.1038","volume":"99","author":[{"given":"Jennifer","family":"C. 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Neurotrauma"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04410-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04410-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04410-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:02:53Z","timestamp":1776848573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04410-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["4410"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-04410-5","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"13 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.K. Wang reported receiving personal fees as a shareholder of Gryphon Bio Inc. and Banyan Biomarkers outside of the submitted work. J.P. de Rivero Vaccari, WD Dietrich, and R.W. Keane are co-founders and managing members of InflamaCORE, LLC, and have licensed patents on inflammasome proteins as biomarkers of injury and disease, as well as on targeting inflammasome proteins for therapeutic purposes. J.C. Munoz Pareja has licensed patents on inflammasome proteins as biomarkers of injury and disease, as well as on targeting inflammasome proteins for therapeutic purposes. J.P. de Rivero Vaccari, W.D. Dietrich, and R.W. Keane are Scientific Advisory Board Members of ZyVersa Therapeutics. None of the remaining authors report interests to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"We obtained approval from the ethical standards committees at the University of Florida (IRB201600237) and the University of Miami (IRB20210352) Institutional Review Boards. We obtained written consent from participants, controls, or their legal representatives to collect blood samples and data from electronic health records (EHR). Modifications to the informed consent process at the University of Florida permitted written consent from participants, controls, or their legal representatives within 72\u2009h of admission. At the University of Miami, we collected blood samples only after previous consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}]}}