{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:57:55Z","timestamp":1785855475562,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["National Institutes of Health NINDSR21NS111389(KAS)"],"award-info":[{"award-number":["National Institutes of Health NINDSR21NS111389(KAS)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS126418 (TAS\/KAS)"],"award-info":[{"award-number":["R01NS126418 (TAS\/KAS)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["G20RR024001"],"award-info":[{"award-number":["G20RR024001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The rate of sudden unexpected death in epilepsy (SUDEP) is ~1 per 1000 patients each year. Terminal events reportedly involve repeated and prolonged apnea, suggesting a failure to autoresuscitate. To better understand the mechanisms and identify novel therapeutics, standardized tests to screen for autoresuscitation efficacy are needed in preclinical SUDEP. To investigate the efficacy of the autoresuscitation response and potential contribution to SUDEP susceptibility, we adapted an anoxia\u2010induced autoresuscitation test. The test was optimized to allow for survival of most wild\u2010type (WT) mice, whereas autoresuscitation failure occurred for most\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, a preclinical model of SUDEP. Using whole\u2010body plethysmography, we assessed ventilatory parameters, gasp\u2013apnea dynamics, and survival in WT,\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , and\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. A proof\u2010of\u2010concept pharmacological rescue was performed using a dual orexin receptor antagonist (DORA). WT mice exhibited robust autoresuscitation (80% survival), whereas only 20% of high\u2010risk\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice survived the anoxic challenge, indicating a 4\u2010fold increase in risk for autoresuscitation failure.\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had disordered ventilatory responses, characterized by increased minute ventilation, tidal volume, and expiratory flow during anoxia.\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice initiated gasping earlier with reduced gasp number, lower gasp frequency, and longer post\u2010gasp apnea durations. In\u2010depth analyses revealed three phases of gasping. Phase III recovery gasping was significantly impaired in\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and they were unable to transition to eupnea. In contrast, low\u2010risk\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice showed intermediate to normal autoresuscitation, respectively. DORA pretreatment improved survival to 80%, restored ventilatory patterns, and normalized gasp\u2013apnea metrics to WT levels. This modified autoresuscitation test provides a reproducible and sensitive approach to probe respiratory vulnerability in preclinical SUDEP models. Our findings identify augmented ventilatory chemosensitivity and impaired autoresuscitation as critical pathophysiological features of SUDEP in\n                    <jats:italic>Kcna1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and support the utility of this test platform for preclinical therapeutic screening and mechanistic discovery.\n                  <\/jats:p>","DOI":"10.1111\/epi.18623","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T14:30:59Z","timestamp":1757428259000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and characterization of an autoresuscitation test for preclinical\n                    <scp>SUDEP<\/scp>\n                    models"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-2495","authenticated-orcid":false,"given":"Shruthi H.","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian E.","family":"Hinman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha B.","family":"Draves","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-3694","authenticated-orcid":false,"given":"Kristina A.","family":"Simeone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-7211","authenticated-orcid":false,"given":"Timothy A.","family":"Simeone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Creighton University School of Medicine  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2021.102907"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.06.037"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(13)70214\u2010X"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109513"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.10.011"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2011.03262.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94999"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000244377"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.119"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.2.677"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00336.2011"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12458"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.3.1098"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.5.2384"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00348"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106592"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16434"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.04.006"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13971"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14660"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5444"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13444"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0b013e3181b7f14d"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c150026"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.05.032"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00329.2009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.10287"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041598"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201014153\u20106"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1288600"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174656"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00014.2018"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274727"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.5.2854"},{"key":"e_1_2_11_36_1","doi-asserted-by":"crossref","unstructured":"NudingSC SegersLS IcemanK O'ConnorR DeanJB ValarezoPA et\u00a0al.Hypoxia evokes a sequence of raphe\u2010pontomedullary network operations for inspiratory drive amplification and gasping.BioRxiv Prepr Serv Biol. 2024:2023.11.07.566027.https:\/\/doi.org\/10.1101\/2023.11.07.566027","DOI":"10.1101\/2023.11.07.566027"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00972.2001"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199712000\u201000025"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.91305.2008"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.023"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00742.2001"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/75776"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/FPHYS.2017.00571"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00265"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004587107"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4186\u201005.2006"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.168260"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00334.2021"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272822"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.05.015"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90416.2008"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18623","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.18623","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:38:45Z","timestamp":1785854325000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/epi.18623"],"URL":"https:\/\/doi.org\/10.1111\/epi.18623","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]},"assertion":[{"value":"2024-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}