{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:50:28Z","timestamp":1792068628658,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Elevated body temperature may increase seizure risk, yet the relationship between thermoregulation and seizures, as well as the underlying mechanisms, remains poorly understood. We investigated whether thermoregulatory control is altered in experimental temporal lobe epilepsy (TLE), as such impairment could reduce the ability of affected individuals to adapt to environmental temperature changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using an adult mouse model of temporal lobe epilepsy (TLE), we longitudinally measured brain temperature before and after epilepsy onset using 7\u2009T\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010magnetic resonance spectroscopy thermometry. The temporal relationship between spontaneous seizures and body temperature fluctuations was assessed using electroencephalographic recordings combined with implanted temperature probes under controlled environmental conditions. Neuronal density, glial reactivity, and transcriptomic profiles were examined in hypothalamic temperature\u2010sensing regions (ventromedial preoptic nucleus [VMPO] and dorsomedial nucleus [DMD]) in epileptic mice and sham mice. Hypothalamic volume was assessed by magnetic resonance imaging (MRI) in both mice and people with epilepsy (PWE). Serum thyroid\u2010stimulating hormone (TSH), T3, and T4 concentrations were measured as indices of hypothalamic\u2013pituitary\u2013thyroid (HPT) axis activity and metabolic thermogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hippocampal temperature increased by ~.5\u20131.5\u00b0C prior to epilepsy onset (3\u2009days postkainate) and remained elevated during chronic epilepsy (1.5\u2009months postkainate). Acutely, body temperature rose from 15\u2009min before to 15\u2009min after spontaneous seizures. Serum T3 and T4 levels were reduced by ~50% without compensatory TSH elevation, indicating HPT axis dysregulation in epileptic mice. Neuronal density in VMPO and DMD decreased by ~20% in chronic epileptic mice versus sham mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05), accompanied by induction of FosB, immune\/inflammatory pathways, and glia reactivity. MRI revealed reduced hypothalamic volume in epileptic mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05), paralleling findings in PWE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Thermoregulatory control is impaired in experimental TLE and is associated with neuronal loss and inflammation in hypothalamic temperature\u2010sensing regions. These findings reveal a link between thermoregulatory dysfunction and epilepsy and highlight that alterations in temperature homeostasis may interact with mechanisms underlying seizure generation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70453","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:02:26Z","timestamp":1787328146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temperature homeostasis disruption and hypothalamic alterations in experimental drug\u2010resistant epilepsy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7481-5198","authenticated-orcid":false,"given":"Rossella","family":"Di Sapia","sequence":"first","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4456-6100","authenticated-orcid":false,"given":"Akash","family":"Bera","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-3381","authenticated-orcid":false,"given":"Omar","family":"Mamad","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics and FutureNeuro Research Ireland Centre RCSI University of Medicine &amp; Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9910-2933","authenticated-orcid":false,"given":"James D.","family":"Mills","sequence":"additional","affiliation":[{"name":"Amsterdam UMC University of Amsterdam  Amsterdam the Netherlands"},{"name":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-8906","authenticated-orcid":false,"given":"Benjamin","family":"Villasana\u2010Salazar","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-0166","authenticated-orcid":false,"given":"Giada","family":"Lavigna","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-2992","authenticated-orcid":false,"given":"Edoardo","family":"Micotti","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Conticello","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9005-2039","authenticated-orcid":false,"given":"Asmin","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering Hawkes Institute, UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-3733","authenticated-orcid":false,"given":"Roberto","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0704-0280","authenticated-orcid":false,"given":"Francesca","family":"Pagani","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-273X","authenticated-orcid":false,"given":"Roberta","family":"Frapolli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-2585","authenticated-orcid":false,"given":"Angelo M.","family":"Lavecchia","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6464-9541","authenticated-orcid":false,"given":"Christodoulos","family":"Xinaris","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-3770","authenticated-orcid":false,"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[{"name":"Amsterdam UMC University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-2393","authenticated-orcid":false,"given":"Andre","family":"Altmann","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering Hawkes Institute, UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9578-018X","authenticated-orcid":false,"given":"Teresa","family":"Ravizza","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-5893","authenticated-orcid":false,"given":"Sanjay M.","family":"Sisodiya","sequence":"additional","affiliation":[{"name":"Research Department of Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-9632","authenticated-orcid":false,"given":"David C.","family":"Henshall","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; 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