{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:17:20Z","timestamp":1781630240441,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR19\u2010CE17\u20100018\u201002"],"award-info":[{"award-number":["ANR19\u2010CE17\u20100018\u201002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Carbamazepine is the first line treatment for patients affected by\n                      <jats:italic>KCNQ2<\/jats:italic>\n                      developmental and epileptic encephalopathy. It is efficient to reduce or stop seizures in this context. However, its effect on the neurodevelopmental outcomes is debated. The aim of this study was to evaluate the efficacy of long\u2010term oral administration of carbamazepine in a mouse model of Kcnq2 dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were treated at weaning and during 70\u2009days. The impact on seizures was measured, and blood samples were collected every week. At 3\u2009months of age, all mice were tested using the Water T\u2010maze and Barnes maze tests to evaluate their cognitive abilities. Brain tissue was collected to measure carbamazepine and carbamazepine\u2010epoxide concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 70\u2009days of carbamazepine treatment, the impact on seizures was strong in the\n                      <jats:italic>Kcnq2<\/jats:italic>\n                      \u2010DEE mice, with 1 out of 12 treated knock\u2010in mice having a seizure compared to 8 out of 13 mice receiving the vehicle. Carbamazepine efficacy on seizures was progressive and correlated to an accumulation of carbamazepine\u2010epoxide in the brain. The cognitive abilities of treated knock\u2010in mice at 3\u2009months of age were similar to those of wild\u2010type mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      In addition to validating this knock\u2010in model as a model of anticonvulsant efficacy, these results reveal that carbamazepine\u2010epoxide accumulates in the brain when given over a long period of time. They also show that chronic treatment with carbamazepine strongly impacts cognitive abilities in a mouse model of\n                      <jats:italic>Kcnq2<\/jats:italic>\n                      \u2010DEE, questioning current treatment strategies in human patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This study evaluated the long\u2010term effects of a treatment with an antiepileptic drug called carbamazepine (CBZ). It was performed in a mouse model of a severe form of genetic epilepsy. The results showed that a chronic treatment with CBZ effectively reduced seizures. Treated mice also showed improved cognitive abilities. An accumulation of a modified form of CBZ was measured in the brain of the treated animals. These findings call for a reevaluation of the long\u2010term effects of CBZ treatment in humans, as the animal data suggest potential beneficial effects that may not yet be fully appreciated in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70087","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T15:04:05Z","timestamp":1752073445000},"page":"1199-1207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010term treatment with carbamazepine restores cognitive abilities in a mouse model of\n                    <i>KCNQ2<\/i>\n                    developmental and epileptic encephalopathy"],"prefix":"10.1002","volume":"10","author":[{"given":"Jordane","family":"Louis","sequence":"first","affiliation":[{"name":"Aix Marseille Univ, Inserm, MMG, U1251  Marseille 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