{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:25:38Z","timestamp":1789050338307,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T00:00:00Z","timestamp":1404345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 257"],"award-info":[{"award-number":["EXC 257"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We tested the hypothesis that interstitial albumin can contribute to pharmacoresistance, which is common among patients with focal epilepsies. These patients often present with an open blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>), resulting in diffusion of drug\u2010binding albumin into the brain interstitial space.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seizure\u2010like events (<jats:styled-content style=\"fixed-case\">SLE<\/jats:styled-content>s) induced by 100\u00a0\u03bc<jats:sc>m<\/jats:sc> 4\u2010aminopyridine (4\u2010<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>) were monitored using extracellular field potential recordings from acute rat entorhinal cortex\u2013hippocampus slices. Effects of standard antiepileptic drugs (phenytoin, valproic acid, carbamazepine, and phenobarbital) were studied in the presence of albumin applied acutely or by intraventricular injection. Unbound antiepileptic drugs (<jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s) were detected by ultrafiltration and high\u2010performance liquid chromatography (<jats:styled-content style=\"fixed-case\">HPLC)<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Contrary to the absence of albumin, conventional <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s failed to suppress <jats:styled-content style=\"fixed-case\">SLE<\/jats:styled-content>s in the rat entorhinal cortex in the presence of albumin. This effect was partially caused by buffering of phenytoin and carbamazepine (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>) by albumin. Increasing <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> concentration from 50\u00a0\u03bc<jats:sc>m<\/jats:sc> to 100\u00a0\u03bc<jats:sc>m<\/jats:sc> resulted in block of <jats:styled-content style=\"fixed-case\">SLE<\/jats:styled-content>s. In slices obtained from animals that were pretreated with intraventricular albumin application 24\u00a0h prior to experiment, <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> suppressed <jats:styled-content style=\"fixed-case\">SLE<\/jats:styled-content>s similar to control slices. We also found that application of serum\u2010like electrolytes transformed <jats:styled-content style=\"fixed-case\">SLE<\/jats:styled-content>s into late recurrent discharges (<jats:styled-content style=\"fixed-case\">LRD<\/jats:styled-content>s), which were no longer responding to <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>A dysfunctional <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> with acute extravasation of serum albumin into the brain's interstitial space could contribute to pharmacoresistance. In such instances, choice of an <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content> with low albumin binding affinity may help in seizure control.<\/jats:p><jats:p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/epi.12713\/supinfo\">here<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12713","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T16:03:07Z","timestamp":1404403387000},"page":"1255-1263","source":"Crossref","is-referenced-by-count":56,"title":["Blood\u2013brain barrier dysfunction can contribute to pharmacoresistance of seizures"],"prefix":"10.1111","volume":"55","author":[{"given":"Seda","family":"Salar","sequence":"first","affiliation":[{"name":"Institute of Neurophysiology Charite\u2010University Medicine Berlin Berlin 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