{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:47:25Z","timestamp":1768549645461,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2018,9,2]],"date-time":"2018-09-02T00:00:00Z","timestamp":1535846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","award":["RAD001MUS246T"],"award-info":[{"award-number":["RAD001MUS246T"]}],"id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007185","name":"University of California, Los Angeles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The present study was designed to examine the potential cellular antiseizure mechanisms of everolimus, a mechanistic target of rapamycin (mTOR) pathway blocker, in pediatric epilepsy cases. Cortical tissue samples obtained from pediatric patients (n\u00a0=\u00a011, ages 0.67\u20136.75\u00a0years) undergoing surgical resections for the treatment of their pharmacoresistant epilepsy were examined electrophysiologically in ex\u00a0vivo slices. The cohort included mTOR\u2010mediated pathologies (tuberous sclerosis complex [TSC] and severe cortical dysplasia [CD]) as well as non\u2013mTOR\u2010mediated pathologies (tumor and perinatal infarct). Bath application of everolimus (2\u00a0\u03bc<jats:sc>m<\/jats:sc>) had practically no effect on spontaneous inhibitory postsynaptic activity. In contrast, long\u2010term application of everolimus reduced spontaneous excitatory postsynaptic activity, burst discharges induced by blockade of \u03b3\u2010aminobutyric acid A (GABA<jats:sub>A<\/jats:sub>) receptors, and epileptiform activity generated by 4\u2010aminopyridine, a K<jats:sup>+<\/jats:sup> channel blocker. The antiseizure effects were more pronounced in TSC and CD cases, whereas in non\u2013mTOR\u2010mediated pathologies, the effects were subtle at best. These results support further clinical trials of everolimus in mTOR pathway\u2013mediated pathologies and emphasize that the effects require sustained exposure over time.<\/jats:p>","DOI":"10.1002\/epi4.12253","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T11:37:41Z","timestamp":1533641861000},"page":"180-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cellular antiseizure mechanisms of everolimus in pediatric tuberous sclerosis complex, cortical dysplasia, and non\u2013mTOR\u2010mediated etiologies"],"prefix":"10.1002","volume":"3","author":[{"given":"Carlos","family":"Cepeda","sequence":"first","affiliation":[{"name":"IDDRC Semel Institute for Neuroscience and Human Behavior UCLA School of Medicine University of California Los Angeles Los Angeles California, 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