{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:48:41Z","timestamp":1790718521270,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T00:00:00Z","timestamp":1476403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 NS065434"],"award-info":[{"award-number":["RO1 NS065434"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN 271201100029C"],"award-info":[{"award-number":["HHSN 271201100029C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Infection with Theiler's murine encephalomyelitis virus (<jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content>) in C57Bl\/6J mice induces acute seizures and development of spontaneous recurrent seizures and behavioral comorbidities weeks later. The present studies sought to determine whether acute therapeutic intervention with an anti\u2010inflammatory\u2013based approach could prevent or modify development of <jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content>\u2010induced long\u2010term behavioral comorbidities. Valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>), in addition to its prototypical anticonvulsant properties, inhibits histone deacetylase (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) activity, which may alter expression of the inflammasome. Minocycline (<jats:styled-content style=\"fixed-case\">MIN<\/jats:styled-content>) has previously demonstrated an antiseizure effect in the <jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content> model via direct anti\u2010inflammatory mechanisms, but the long\u2010term effect of <jats:styled-content style=\"fixed-case\">MIN<\/jats:styled-content> treatment on the development of chronic behavioral comorbidities is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice infected with <jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content> were acutely administered <jats:styled-content style=\"fixed-case\">MIN<\/jats:styled-content> (50 mg\/kg, b.i.d. and q.d.) or <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> (100 mg\/kg, q.d.) during the 7\u2010day viral infection period. Animals were evaluated for acute seizure severity and subsequent development of chronic behavioral comorbidities and seizure threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> reduced the proportion of mice with seizures, delayed onset of symptomatic seizures, and reduced seizure burden during the acute infection. This was in contrast to the effects of administration of once\u2010daily <jats:styled-content style=\"fixed-case\">MIN<\/jats:styled-content>, which did not affect the proportion of mice with seizures or delay onset of acute symptomatic seizures. However, <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated mice were no different from vehicle (<jats:styled-content style=\"fixed-case\">VEH<\/jats:styled-content>)\u2013treated mice in long\u2010term behavioral outcomes, including open field activity and seizure threshold. Once\u2010daily <jats:styled-content style=\"fixed-case\">MIN<\/jats:styled-content> treatment, despite no effect on the maximum observed Racine stage seizure severity, was associated with improved long\u2010term behavioral outcomes and normalized seizure threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Acute seizure control alone is insufficient to modify chronic disease comorbidities in the <jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content> model. This work further supports the role of an inflammatory response in the development of chronic behavioral comorbidities and further highlights the utility of this platform for the development of mechanistically novel pharmacotherapies for epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13577","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T11:19:28Z","timestamp":1476443968000},"page":"1958-1967","source":"Crossref","is-referenced-by-count":55,"title":["Acute treatment with minocycline, but not valproic acid, improves long\u2010term behavioral outcomes in the Theiler's virus model of temporal lobe epilepsy"],"prefix":"10.1111","volume":"57","author":[{"given":"Melissa L.","family":"Barker\u2010Haliski","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Anticonvulsant Drug Development Program University of Utah Salt Lake City Utah U.S.A"},{"name":"Department of Pharmacy School of Pharmacy University of Washington Seattle Washington U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor D.","family":"Heck","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Anticonvulsant Drug Development Program University of Utah Salt Lake City Utah U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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