{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:20:47Z","timestamp":1792095647414,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS100064"],"award-info":[{"award-number":["U54NS100064"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post\u2010traumatic epilepsy (PTE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adult male Sprague\u2013Dawley rats (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009245) were randomized to lateral fluid\u2010percussion\u2013induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video\u2010electroencephalography (vEEG) was performed on the seventh post\u2010injury month to detect spontaneous seizures. Tail vein plasma collected 48\u2009h after TBI for miRNA analysis was available from 209 vEEG monitored animals (45 sham, 164 TBI [32 with epilepsy]). Based on small RNA sequencing and previous data, the seven most promising brain enriched miRNAs (miR\u2010183\u20105p, miR\u2010323\u20103p, miR\u2010434\u20103p, miR\u20109a\u20103p, miR\u2010124\u20103p, miR\u2010132\u20103p, and miR\u2010212\u20103p) were validated by droplet digital polymerase chain reaction (ddPCR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All seven plasma miRNAs differentiated between TBI and sham\u2010operated rats. None of the seven miRNAs differentiated TBI rats that did and did not develop epilepsy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u2009.05), or rats with \u22653 vs &lt;3 seizures in a month (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u2009.05). However, miR\u2010212\u20103p differentiated rats that developed epilepsy with seizure clusters (i.e., \u22653 seizures within 24\u2009h) from those without seizure clusters (.34\u2009\u00b1\u2009.14 vs .60\u2009\u00b1\u2009.34, adj.\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05) with an area under the curve (AUC) of .81 (95% confidence interval [CI] .65\u2013.97,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01, 64% sensitivity, 95% specificity). Lack of elevation in miR\u2010212\u20103p also differentiated rats that developed epilepsy with seizure clusters from all other TBI rats (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009146, .34\u2009\u00b1\u2009.14 vs .55\u2009\u00b1\u2009.31,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01) with an AUC of .74 (95% CI .61\u2013.87,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01, 82% sensitivity, 62% specificity). Glmnet analysis identified a combination of miR\u2010212\u20103p and miR\u2010132\u20103p as an optimal set to differentiate TBI rats with vs without seizure clusters (cross\u2010validated AUC .75, 95% CI .47\u2013.92,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>miR\u2010212\u20103p alone or in combination with miR\u2010132\u20103p shows promise as a translational prognostic biomarker for the development of severe PTE with seizure clusters.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18219","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T14:13:09Z","timestamp":1733926389000},"page":"870-885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Plasma\n                    <scp>microRNAs<\/scp>\n                    as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain injury\u2014\n                    <scp>EpiBioS4Rx<\/scp>\n                    Project 1 study"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-5240","authenticated-orcid":false,"given":"Mette","family":"Heiskanen","sequence":"first","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-5632","authenticated-orcid":false,"given":"Xavier Ekolle","family":"Ndode\u2010Ekane","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-4654","authenticated-orcid":false,"given":"Idrish","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Medicine, the Royal Melbourne Hospital The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-5615","authenticated-orcid":false,"given":"Cesar","family":"Santana\u2010Gomez","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6151-3510","authenticated-orcid":false,"given":"Noora","family":"Puhakka","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini Das","family":"Gupta","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Andrade","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"Immonen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-9415","authenticated-orcid":false,"given":"Pablo","family":"Casillas\u2010Espinosa","sequence":"additional","affiliation":[{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Medicine, the Royal Melbourne Hospital The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9353-6079","authenticated-orcid":false,"given":"Eppu","family":"Manninen","sequence":"additional","affiliation":[{"name":"A. I. 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