{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:29Z","timestamp":1787014169290,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004385","name":"Universiteit Gent","doi-asserted-by":"publisher","award":["BOFIOP24j2016000601"],"award-info":[{"award-number":["BOFIOP24j2016000601"]}],"id":[{"id":"10.13039\/501100004385","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S30017N"],"award-info":[{"award-number":["1S30017N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S74519N"],"award-info":[{"award-number":["1S74519N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1216520N"],"award-info":[{"award-number":["1216520N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["IOF C32\/15\/031"],"award-info":[{"award-number":["IOF C32\/15\/031"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>One third of epilepsy patients do not become seizure\u2010free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long\u2010term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Epileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno\u2010associated viral vector encoding the inhibitory DREADD hM4D(Gi), preceded by a cell\u2010specific promotor targeting excitatory neurons. The effect of clozapine\u2010mediated DREADD activation on dentate gyrus evoked potentials and spontaneous electrographic seizures was evaluated. Animals were systemically treated with single (.1\u00a0mg\/kg\/24\u00a0h) or repeated (.1\u00a0mg\/kg\/6\u00a0h) injections of clozapine. In addition, long\u2010term continuous release of clozapine and olanzapine (2.8\u00a0mg\/kg\/7\u00a0days) using implantable minipumps was evaluated. All treatments were administered during the chronic epileptic phase and between 1.5 and 13.5\u00a0months after viral transduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the DREADD group, dentate gyrus evoked potentials were inhibited after clozapine treatment. Only in DREADD\u2010expressing animals, clozapine reduced seizure frequency during the first 6 h postinjection. When administered repeatedly, seizures were suppressed during the entire day. Long\u2010term treatment with clozapine and olanzapine both resulted in significant seizure\u2010suppressing effects for multiple days. Histological analysis revealed DREADD expression in both hippocampi and some cortical regions. However, lesions were also detected at the site of vector injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This study shows that inhibition of the hippocampus using chemogenetics results in potent seizure\u2010suppressing effects in the intraperitoneal kainic acid rat model, even 1 year after viral transduction. Despite a need for further optimization, chemogenetic neuromodulation represents a promising treatment prospect for temporal lobe epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16840","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T22:01:54Z","timestamp":1613253714000},"page":"659-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Long\u2010term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-929X","authenticated-orcid":false,"given":"Marie\u2010Gabrielle","family":"Goossens","sequence":"first","affiliation":[{"name":"4BRAIN Department of Head and Skin Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Boon","sequence":"additional","affiliation":[{"name":"4BRAIN Department of Head and Skin Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wytse","family":"Wadman","sequence":"additional","affiliation":[{"name":"4BRAIN Department of Head and Skin Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Van den Haute","sequence":"additional","affiliation":[{"name":"Laboratory for Neurobiology and Gene Therapy Center for Molecular Medicine and Leuven Brain Institute KU Leuven Leuven Belgium"},{"name":"Leuven Viral Vector Core Center for Molecular Medicine KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Baekelandt","sequence":"additional","affiliation":[{"name":"Laboratory for Neurobiology and Gene Therapy Center for Molecular Medicine and Leuven Brain Institute KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain G.","family":"Verstraete","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences Ghent University Ghent Belgium"},{"name":"Department of Laboratory Medicine Ghent University Hospital Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristl","family":"Vonck","sequence":"additional","affiliation":[{"name":"4BRAIN Department of Head and Skin Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars E.","family":"Larsen","sequence":"additional","affiliation":[{"name":"4BRAIN Department of Head and Skin Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-9896","authenticated-orcid":false,"given":"Mathieu","family":"Sprengers","sequence":"additional","affiliation":[{"name":"4BRAIN Department of Head 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