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We evaluated the associations between circulating blood biomarkers of neuronal, glial, and synaptic injury and the subsequent development of PTE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prespecified subanalysis was conducted within a randomized phase III clinical trial of biperiden in adults with acute TBI. Participants were randomly assigned to receive intravenous biperiden (4\u2009mg every 6\u2009h for 10\u2009days) or placebo. Serum samples collected during the acute (1\u201315\u2009days) or chronic (90\u2013270\u2009days) post\u2010injury periods were analyzed for total tau (t\u2010Tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C\u2010terminal hydrolase L1 (UCHL1), and synaptosomal\u2010associated protein 25 (SNAP25) using an ultrasensitive single\u2010molecule array (SiMoA) platform. Exploratory multivariable analyses were performed to assess associations between biomarker concentrations and PTE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 123 patients were enrolled. Blood samples were obtained from 58 participants (60 serum samples) for biomarker analysis, with most participants contributing a single sample and only two participants providing paired samples collected at different post\u2010injury time points. The median age was 42\u2009years and 48 participants (82.8%) were men. Only six patients (10.3%) developed PTE during follow\u2010up, four in the biperiden group and two in the placebo group. NfL and GFAP concentrations varied according to injury severity and sampling period. Compared with patients who did not develop PTE, those who later developed epilepsy showed descriptively lower NfL and SNAP25 and higher t\u2010Tau, GFAP, and UCHL1 concentrations. SNAP25 was detected in serum for the first time; however, concentrations were frequently below the assay's lower limit of quantification, limiting interpretation of this biomarker and no association with epilepsy development was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Circulating biomarkers reflecting axonal, glial, and synaptic injury provide a descriptive characterization of biological processes following TBI. Given the limited number of PTE events, these analyses are exploratory and hypothesis generating. Further studies are needed to evaluate whether blood\u2010based biomarkers can reliably identify individuals at risk of post\u2010traumatic epileptogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70372","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:37:16Z","timestamp":1790069836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating blood biomarkers after traumatic brain injury: A subanalysis of the biperiden phase\n                    <scp>III<\/scp>\n                    randomized, double\u2010blind clinical trial (\n                    <scp>NCT01048138<\/scp>\n                    )"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-2283","authenticated-orcid":false,"given":"Michele Longoni","family":"Cali\u00f3","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology, Department of Physiology 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