{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:34:27Z","timestamp":1789598067517,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>) leakage may play a pro\u2010epileptogenic role after status epilepticus. In the accompanying contrast\u2010enhanced magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">CE\u2010MRI<\/jats:styled-content>) study we showed that the mammalian target of rapamycin (<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>) inhibitor rapamycin reduced <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seven weeks after kainic acid\u2013induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> integrity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin\u2010treated rats compared to vehicle\u2010treated rats. In vitro studies showed that rapamycin could attenuate <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1\u2010induced endothelial barrier breakdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These data suggest that rapamycin improves <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13245","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T13:39:32Z","timestamp":1450791572000},"page":"70-78","source":"Crossref","is-referenced-by-count":42,"title":["Blood\u2013brain barrier leakage after status epilepticus in rapamycin\u2010treated rats <scp>II<\/scp>: Potential mechanisms"],"prefix":"10.1111","volume":"57","author":[{"given":"Erwin A.","family":"van 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