Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy
| dc.contributor.author | Gudenschwager-Basso, Erwin Kristobal | en |
| dc.contributor.author | Shandra, Oleksii | en |
| dc.contributor.author | Volanth, Troy | en |
| dc.contributor.author | Patel, Dipan C. | en |
| dc.contributor.author | Kelly, Colin | en |
| dc.contributor.author | Browning, Jack L. | en |
| dc.contributor.author | Wei, Xiaoran | en |
| dc.contributor.author | Harris, Elizabeth A. | en |
| dc.contributor.author | Mahmutovic, Dzenis | en |
| dc.contributor.author | Kaloss, Alexandra M. | en |
| dc.contributor.author | Correa, Fernanda Guilhaume | en |
| dc.contributor.author | Decker, Jeremy | en |
| dc.contributor.author | Maharathi, Biswajit | en |
| dc.contributor.author | Robel, Stefanie | en |
| dc.contributor.author | Sontheimer, Harald | en |
| dc.contributor.author | VandeVord, Pamela J. | en |
| dc.contributor.author | Olsen, Michelle L. | en |
| dc.contributor.author | Theus, Michelle H. | en |
| dc.date.accessioned | 2023-04-27T14:53:53Z | en |
| dc.date.available | 2023-04-27T14:53:53Z | en |
| dc.date.issued | 2023-04-25 | en |
| dc.date.updated | 2023-04-27T13:50:53Z | en |
| dc.description.abstract | 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—a structure that is highly susceptible to injury—has 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 2–4 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<sup>+</sup>) vs. those animals that did not (PTE<sup>−</sup>), 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<sup>+</sup> compared to PTE<sup>−</sup> mice. We uniquely identified <i>Cst3</i> as a PTE<sup>+</sup>-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE<sup>+</sup> 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. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Gudenschwager-Basso, E.K.; Shandra, O.; Volanth, T.; Patel, D.C.; Kelly, C.; Browning, J.L.; Wei, X.; Harris, E.A.; Mahmutovic, D.; Kaloss, A.M.; Correa, F.G.; Decker, J.; Maharathi, B.; Robel, S.; Sontheimer, H.; VandeVord, P.J.; Olsen, M.L.; Theus, M.H. Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy. Cells 2023, 12, 1248. | en |
| dc.identifier.doi | https://doi.org/10.3390/cells12091248 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/114827 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | traumatic brain injury | en |
| dc.subject | hippocampus | en |
| dc.subject | granular neurons | en |
| dc.subject | neuroblasts | en |
| dc.subject | seizures | en |
| dc.subject | epilepsy | en |
| dc.subject | PTE | en |
| dc.title | Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy | en |
| dc.title.serial | Cells | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |