{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:46:07Z","timestamp":1790394367248,"version":"4.1.0"},"reference-count":38,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL104101"],"award-info":[{"award-number":["HL104101"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL137094"],"award-info":[{"award-number":["HL137094"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["134132"],"award-info":[{"award-number":["134132"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["F31 NS120467"],"award-info":[{"award-number":["F31 NS120467"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["F31 HL167553"],"award-info":[{"award-number":["F31 HL167553"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,22]]},"abstract":"<jats:p>\n                    Dravet syndrome (DS) is an early-onset epilepsy caused by loss-of-function mutations in the\n                    <jats:italic>SCN1A<\/jats:italic>\n                    gene, which encodes Nav1.1 channels that preferentially regulate activity of inhibitory neurons early in development. DS is associated with a high incidence of sudden unexpected death in epilepsy (SUDEP) by a mechanism that may involve respiratory failure. Evidence also shows that loss of\n                    <jats:italic>Scn1a<\/jats:italic>\n                    impaired activity of neurons in the retrotrapezoid nucleus (RTN) that regulate breathing in response to CO\n                    <jats:sub>2<\/jats:sub>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    , suggesting breathing problems precede seizures and serve as a biomarker of SUDEP. Consistent with this, we showed that\n                    <jats:italic>\n                      Scn1a\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited a blunted ventilatory response to CO\n                    <jats:sub>2<\/jats:sub>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    prior to overt seizure activity that worsened with disease progression. Later in development, some\n                    <jats:italic>\n                      Scn1a\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice also showed a blunted ventilatory response to hypoxia. Importantly, the severity of respiratory problems correlated with mortality. We also found that pharmacological activation of Nav1.1 rescued activity deficits of RTN neurons in\n                    <jats:italic>\n                      Scn1a\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. We conclude that disordered breathing may be an early biomarker of SUDEP in DS, and at the cellular level, loss of\n                    <jats:italic>Scn1a<\/jats:italic>\n                    disrupts RTN neurons by mechanisms involving disinhibition and pharmacological activation of Nav1.1 to reestablish inhibitory control of RTN neurons rescues activity deficits.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184231","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T16:00:34Z","timestamp":1757433634000},"source":"Crossref","is-referenced-by-count":5,"title":["Developmental progression of respiratory dysfunction in a mouse model of Dravet syndrome"],"prefix":"10.1172","volume":"10","author":[{"given":"Brenda M.","family":"Milla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliandra N.","family":"da 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