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During the 6th postinjury month, rats underwent 30\u2009days of continuous video\u2010electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T<jats:sub>2<\/jats:sub> magnetic resonance imaging were performed to assess comorbidities and lesion severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 112 TBI rats, 25% (28\/112) developed epilepsy (TBI+) and 75% (84\/112) did not (TBI\u2212). Plasma pNF\u2010H concentrations were higher in TBI+ rats than in TBI\u2212 rats (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Receiver operating characteristic curve analysis indicated that plasma pNF\u2010H concentration distinguished TBI+ rats from TBI\u2212 rats (area under the curve [AUC] = .647, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (\u22653 seizures\/month) with all other TBI rats (AUC = .732, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01). Plasma pNF\u2010H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Higher plasma pNF\u2010H concentration on D2 after TBI correlated with lower neuroscores on D2 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), D6 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), and D14 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01). Higher pNF\u2010H concentration on D2 correlated with greater T<jats:sub>2<\/jats:sub> signal abnormality volume on D2 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and D7 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) and larger cortical lesion area on D182 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01). Plasma pNF\u2010H concentration on D2 did not correlate with Morris water maze performance on D37\u2013D39.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Plasma pNF\u2010H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18149","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T15:45:24Z","timestamp":1728920724000},"page":"3703-3716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plasma neurofilament heavy chain is a prognostic biomarker for the development of severe epilepsy after experimental traumatic brain injury"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-5240","authenticated-orcid":false,"given":"Mette","family":"Heiskanen","sequence":"first","affiliation":[{"name":"A. 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