{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:59:03Z","timestamp":1785448743954,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,12]]},"group-title":"Neuroscience","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01NS102937"],"award-info":[{"award-number":["R01NS102937"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MU NextGen Precision Health","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}]},{"name":"MU Mizzou Forward","award":["Undergraduate Research Training Grant"],"award-info":[{"award-number":["Undergraduate Research Training Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Sudden unexpected death in Epilepsy (SUDEP) is the leading cause of death in patients with Epilepsy. Although SUDEP results from cardiorespiratory arrest, it\u2019s underlying mechanisms are poorly understood. Considering the significant association between stress-related disorders and Epilepsy, we hypothesized that stress exaggerates autonomic reflexes critical in cardiorespiratory function and that these exaggerated reflexes increase susceptibility to SUDEP. Experiments were performed using a novel mouse model of SUDEP where hyperreactivity of central corticotropin-releasing hormone (CRH) neurons (\n                  <jats:italic>Kcc2\/Crh<\/jats:italic>\n                  ) predisposes mice to SUDEP in the weeks following seizure induction based on the ventral intrahippocampal kainate (vIHKA) model of chronic Epilepsy. In our study, the vIHKA model was employed in both wild-type (WT) and\n                  <jats:italic>Kcc2\/Crh<\/jats:italic>\n                  mice while they were monitored with EEG and ECG using in vivo telemetry and underwent terminal autonomic reflex testing at time points when mortality peaked and plateaued. A resting tachycardia developed by one week following vIHKA injection but subsided by day 30 in both WT and\n                  <jats:italic>Kcc2\/Crh<\/jats:italic>\n                  mice. During spontaneous seizures,\n                  <jats:italic>Kcc2\/Crh<\/jats:italic>\n                  mice had more pronounced reflex-like ictal bradycardias compared to WT controls that notably occurred prior (\u223c10 sec) to seizure termination. vIHKA injection promoted time-dependent exaggeration of autonomic reflexes, with\n                  <jats:italic>Kcc2\/Crh<\/jats:italic>\n                  mice exhibiting robust autonomic disturbances compared to WT controls, including a pronounced serotonin-mediated Bezold Jarisch reflex. Taken together, our findings indicate that increased autonomic disturbance burden parallels time-dependent SUDEP susceptibility in mice with hyperreactive stress circuits.\n                <\/jats:p>","DOI":"10.1101\/2025.11.11.687816","type":"posted-content","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:20:12Z","timestamp":1763126412000},"source":"Crossref","is-referenced-by-count":1,"title":["Autonomic reflex plasticity associates with time-dependent SUDEP susceptibility in a murine model with hyperreactive stress circuits"],"prefix":"10.64898","author":[{"given":"Sandy E.","family":"Saunders","sequence":"first","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylie E.","family":"Dow","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Bostic","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery A.","family":"Boychuk","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Maguire","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Tufts University, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carie 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