{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:33:29Z","timestamp":1787848409701,"version":"build-2784847793"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005671","name":"Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa e \u00e0 Inova\u00e7\u00e3o Tecnol\u00f3gica do Estado de Sergipe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit an abnormal excitatory \/ inhibitory balance. In this study, we examine how brain injury alters susceptibility to chemically-induced seizures in C57Bl\/6J mice, and if pharmacological enhancement of glutamate transporters can reduce chronic post-traumatic seizures. We found that controlled cortical impact (CCI) mice display delayed susceptibility to pentylenetetrazol (PTZ)-induced seizures. While CCI mice have no change in seizure susceptibility at 7d post-injury (dpi), at 70dpi they have reduced latency to PTZ-induced seizure onset, higher seizure frequency and longer seizure duration. Quantification of glutamate transporter mRNA showed that levels of<jats:italic>Scl1a2<\/jats:italic>and<jats:italic>Scl1a3<\/jats:italic>mRNA were increased at 7dpi, but significantly decreased at 70dpi. To test if increased levels of glutamate transporters can ameliorate delayed-onset seizure susceptibility in TBI mice, we exposed a new cohort of mice to CCI and administered ceftriaxone (200mg\/kg\/day) for 14d from 55-70dpi. We found that ceftriaxone significantly increased<jats:italic>Scl1a2<\/jats:italic>and<jats:italic>Scl1a3<\/jats:italic>in CCI mouse brain at 70dpi, and prevented the susceptibility of CCI mice to PTZ-induced seizures. This study demonstrates cortical impact can induce a delayed-onset seizure phenotype in mice. Delayed (55dpi) ceftriaxone treatment enhances glutamate transporter mRNA in the CCI brain, and reduces PTZ-induced seizures in CCI mice.<\/jats:p>","DOI":"10.1371\/journal.pone.0288363","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T17:32:29Z","timestamp":1689269549000},"page":"e0288363","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Delayed treatment with ceftriaxone reverses the enhanced sensitivity of TBI mice to chemically-induced seizures"],"prefix":"10.1371","volume":"18","author":[{"given":"Simone A. 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