Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy

dc.contributor.authorBrowning, Jack L.en
dc.contributor.authorWilson, Kelsey A.en
dc.contributor.authorShandra, Oleksiien
dc.contributor.authorWei, Xiaoranen
dc.contributor.authorMahmutovic, Dzenisen
dc.contributor.authorMaharathi, Biswajiten
dc.contributor.authorRobel, Stefanieen
dc.contributor.authorVandeVord, Pamela J.en
dc.contributor.authorOlsen, Michelle L.en
dc.date.accessioned2024-03-12T17:50:27Zen
dc.date.available2024-03-12T17:50:27Zen
dc.date.issued2024-03-01en
dc.date.updated2024-03-12T16:37:58Zen
dc.description.abstractTraumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances and PTE; however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a mouse model of repeated bTBI (rbTBI), this study addresses this gap in the knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up to four months. Following this period, we collected cortex and hippocampus tissues from three groups of mice: those with post-traumatic epilepsy (PTE<sup>+</sup>), those without epilepsy (PTE<sup>&minus;</sup>), and the control group (sham). Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE<sup>+</sup> and PTE<sup>&minus;</sup> relative to sham. Focusing on protein pathways unique to PTE<sup>+</sup>, pathways related to mitochondrial function, post-translational modifications, and transport were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in the epileptic tissue relative to PTE<sup>&minus;</sup>. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequelae following rbTBI.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBrowning, J.L.; Wilson, K.A.; Shandra, O.; Wei, X.; Mahmutovic, D.; Maharathi, B.; Robel, S.; VandeVord, P.J.; Olsen, M.L. Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy. Int. J. Mol. Sci. 2024, 25, 2880.en
dc.identifier.doihttps://doi.org/10.3390/ijms25052880en
dc.identifier.urihttps://hdl.handle.net/10919/118315en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleApplying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsyen
dc.title.serialInternational Journal of Molecular Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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