{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:56:07Z","timestamp":1790441767011,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","award":["2014\/R\/21"],"award-info":[{"award-number":["2014\/R\/21"]}],"id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008222","name":"Universit\u00e9 de Montpellier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008222","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>\n                    Immune changes occur in experimental and clinical epilepsy. Here, we tested the hypothesis that during epileptogenesis and spontaneous recurrent seizures (SRS) an impairment of the endogenous anti\u2010inflammatory pathway glucocorticoid receptor (GR)\u2010annexin A1 (ANXA1) occurs. By administrating exogenous ANXA1, we studied whether pharmacological potentiation of the anti\u2010inflammatory response modifies seizure activity and pathophysiology. We used an\n                    <jats:italic>in vivo<\/jats:italic>\n                    model of temporal lobe epilepsy based on intrahippocampal kainic acid (KA) injection. Video\u2010electroencephalography, molecular biology analyses on brain and peripheral blood samples, and pharmacological investigations were performed in this model. Human epileptic cortices presenting type II focal cortical dysplasia (IIa and b), hippocampi with or without hippocampal sclerosis (HS), and available controls were used to study ANXA1 expression. A decrease of phosphorylated (phospho\u2010) GR and phospho\u2010GR\/tot\u2010GR protein expression occurred in the hippocampus during epileptogenesis. Downstream to GR, the anti\u2010inflammatory protein ANXA1 remained at baseline levels while inflammation installed and endured. In peripheral blood, ANXA1 and corticosterone levels showed no significant modifications during disease progression except for an early and transient increase poststatus epilepticus. These results indicate inadequate ANXA1 engagement over time and in these experimental conditions. By analyzing human brain specimens, we found that where significant inflammation exists, the pattern of ANXA1 immunoreactivity was abnormal because the typical perivascular ANXA1 immunoreactivity was reduced. We next asked whether potentiation of the endogenous anti\u2010inflammatory mechanism by ANXA1 administration modifies the disease pathophysiology. Although with varying efficacy, administration of exogenous ANXA1 somewhat reduced the time spent in seizure activity as compared to saline. These results indicate that the anti\u2010inflammatory GR\u2010ANXA1 pathway is defective during experimental seizure progression. The prospect of pharmacologically restoring or potentiating this endogenous anti\u2010inflammatory mechanism as an add\u2010on therapeutic strategy for specific forms of epilepsy is proposed.\u2014Zub, E., Canet, G., Garbelli, R., Blaquiere, M., Rossini, L., Pastori, C., Sheikh, M., Reutelingsperger, C., Klement, W., de Bock, F., Audinat, E., Givalois, L., Solito, E., Marchi, N. The GR\u2010ANXA1 pathway is a pathological player and a candidate target in epilepsy. FASEB J. 33, 13998\u201014009 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901596r","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T18:03:04Z","timestamp":1571248984000},"page":"13998-14009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The GR\u2010ANXA1 pathway is a pathological player and a candidate target in epilepsy"],"prefix":"10.1096","volume":"33","author":[{"given":"Emma","family":"Zub","sequence":"first","affiliation":[{"name":"Laboratory of Cerebrovascular and Glia Research Department of Neuroscience Institute of Functional Genomics Unit\u00e9 Mixtes de Recherche (UMR) 5203 Centre National de la Recherche Scientifique (CNRS)\u2010Unit\u00e9 1191 INSERM University of Montpellier Montpellier 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Cardiovascular Research Institute, Maastricht University Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Klement","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebrovascular and Glia Research Department of Neuroscience Institute of Functional Genomics Unit\u00e9 Mixtes de Recherche (UMR) 5203 Centre National de la Recherche Scientifique (CNRS)\u2010Unit\u00e9 1191 INSERM University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"de Bock","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebrovascular and Glia Research Department of Neuroscience Institute of Functional Genomics Unit\u00e9 Mixtes de Recherche (UMR) 5203 Centre National de la Recherche Scientifique (CNRS)\u2010Unit\u00e9 1191 INSERM University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Audinat","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebrovascular and Glia Research Department of Neuroscience Institute of Functional Genomics Unit\u00e9 Mixtes de Recherche (UMR) 5203 Centre National de la Recherche Scientifique (CNRS)\u2010Unit\u00e9 1191 INSERM University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Givalois","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms in Neurodegenerative Diseases, INSERM Unite 1198 University of Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egle","family":"Solito","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Naples 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