{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:36:04Z","timestamp":1790274964328,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CURE Epilepsy","award":["W81XWH-15-2-0069"],"award-info":[{"award-number":["W81XWH-15-2-0069"]}]},{"name":"United States Army Medical Research and Materiel Command, Department of Defense (DoD)","award":["W81XWH-15-2-0069"],"award-info":[{"award-number":["W81XWH-15-2-0069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus\u2014a structure that is highly susceptible to injury\u2014has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24\/7 EEG video analysis at 2\u20134 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by unbiased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching, and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-Seq were performed to determine differential gene expression in animals that developed post-traumatic epilepsy (PTE+) vs. those animals that did not (PTE\u2212), which may be associated with epileptogenesis. Results: CCI injury resulted in 37% PTE incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE\u2212 mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE+ hilus. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.<\/jats:p>","DOI":"10.3390\/cells12091248","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T01:16:25Z","timestamp":1682471785000},"page":"1248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-9992","authenticated-orcid":false,"given":"Erwin Kristobal","family":"Gudenschwager-Basso","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-3312","authenticated-orcid":false,"given":"Oleksii","family":"Shandra","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"Department of Biomedical Engineering, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Volanth","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipan C.","family":"Patel","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-532X","authenticated-orcid":false,"given":"Colin","family":"Kelly","sequence":"additional","affiliation":[{"name":"Translational Biology Medicine and Health Graduate Program, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3102-0667","authenticated-orcid":false,"given":"Jack L.","family":"Browning","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzenis","family":"Mahmutovic","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-2320","authenticated-orcid":false,"given":"Alexandra M.","family":"Kaloss","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-5283","authenticated-orcid":false,"given":"Fernanda Guilhaume","family":"Correa","sequence":"additional","affiliation":[{"name":"Translational Biology Medicine and Health Graduate Program, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Mechanics, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswajit","family":"Maharathi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6716-3670","authenticated-orcid":false,"given":"Stefanie","family":"Robel","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Sontheimer","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech, 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