{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T09:37:45Z","timestamp":1793007465748,"version":"4.5.0"},"reference-count":162,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Netw. Physiol."],"abstract":"<jats:p>Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality and is typically characterized by a terminal cascade of respiratory failure, cardiac arrhythmia, and cerebral suppression. Although epilepsy has long been regarded as a neuron-proprietary disorder, accumulating evidence indicates that glial cells, particularly astrocytes, play pivotal roles in both epileptogenesis and the progression to SUDEP. Astrocytes maintain neuronal homeostasis by regulating extracellular potassium through the inwardly rectifying potassium channel Kir4.1 and by clearing extracellular glutamate. Impairment of these homeostatic functions, together with reactive astrogliosis and the release of pro-inflammatory cytokines, including interleukin-1\u03b2 and tumor necrosis factor-\u03b1, promotes neuronal hypersynchrony and lowers the seizure threshold. Severe hypoxia, a critical consequence in respiratory disturbance, sequentially activates microglia and astrocytes, thereby facilitating seizure generation and further depression of respiratory output. Furthermore, seizure propagation or spreading depolarization into brainstem respiratory centers, including the pre-B\u00f6tzinger complex and the nucleus tractus solitarius, may induce fatal central apnea or upper airway obstruction. Neuropathological evidence of neuronal and astrocytic loss in the ventrolateral medulla further suggests that chronic brainstem dysfunction increases susceptibility to respiratory failure. Experimental studies demonstrate that pharmacological inhibition of astrocytic activation delays hypoxia-induced seizures and respiratory arrest, highlighting astrocytes as a potential therapeutic target. A deeper understanding of neuron-glia interactions within the active neural milieu will facilitate the development of novel preventive strategies for SUDEP.<\/jats:p>","DOI":"10.3389\/fnetp.2026.1955271","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:27:10Z","timestamp":1790839630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytes at the interface of peri-ictal breathing dysfunction and SUDEP"],"prefix":"10.3389","volume":"6","author":[{"given":"Isato","family":"Fukushi","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Aomori University of Health and Welfare","place":["Aomori, Japan"]},{"name":"Clinical Research Center, Murayama Medical Center","place":["Musashimurayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isamu","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, Hirosaki University of Health and Welfare","place":["Hirosaki, Japan"]},{"name":"Department of Advanced Technology in Medicine, Institute of Biomedical Engineering, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczyslaw","family":"Pokorski","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, University of Opole","place":["Opole, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Okada","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Murayama Medical Center","place":["Musashimurayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"282ra246","DOI":"10.1126\/scitranslmed.aaa4050","article-title":"Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models","volume":"7","author":"Aiba","year":"2015","journal-title":"Sci. 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