{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:18:10Z","timestamp":1771633090881,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T00:00:00Z","timestamp":1573257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000295","name":"Epilepsy Research UK","doi-asserted-by":"publisher","award":["James Lewis Foundation P1402"],"award-info":[{"award-number":["James Lewis Foundation P1402"]}],"id":[{"id":"10.13039\/501100000295","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre\u2010B\u00f6tzinger complex, leading to sudden death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Urethane\u2010anesthetized female Long\u2010Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre\u2010B\u00f6tzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty\u2010two of thirty\u2010one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas. Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse. Cardiac activity continued for tens of seconds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP).<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16374","type":"journal-article","created":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T08:54:25Z","timestamp":1573289665000},"page":"2346-2358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0106-4412","authenticated-orcid":false,"given":"John G. R.","family":"Jefferys","sequence":"first","affiliation":[{"name":"Weldon School of Biomedical Engineering Purdue University West Lafayette IN USA"},{"name":"Department of Pharmacology Oxford University Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad A.","family":"Arafat","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering Purdue University West Lafayette IN USA"},{"name":"Department of Electrical and Computer Engineering Purdue University West Lafayette IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4791-4593","authenticated-orcid":false,"given":"Pedro P.","family":"Irazoqui","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering Purdue University West Lafayette IN USA"},{"name":"Department of Electrical and Computer Engineering Purdue University West Lafayette IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7329-4607","authenticated-orcid":false,"given":"Thelma A.","family":"Lovick","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering Purdue University West Lafayette IN USA"},{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30158-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70214-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01860.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01545.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2584-15.2016"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.08.004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.01.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa4050"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605216113"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy325"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.10.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01070.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(90)90006-K"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13765"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00849.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-013-0697-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2016.05.011"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-016-0475-y"},{"key":"e_1_2_8_20_1","first-page":"271","article-title":"Urethane\u2010induced hyperglycemia","volume":"21","author":"Wang MY","year":"2000","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(88)90077-8"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9008-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.09.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3874-12.2013"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(98)00269-8"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1109\/TNSRE.2019.2932032"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183619"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2006.07.007"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4058-14.2015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(92)90052-X"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4331-15.2016"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-018-0602-z"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00588"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.6.2052"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2018.03.004"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00350.2017"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2001001200013"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.10193.1"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(81)90028-8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.05.005"},{"key":"e_1_2_8_41_1","first-page":"G91","article-title":"Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats","volume":"260","author":"White RL","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00490-X"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16645113"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348941112001111"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.16374","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16374","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16374","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T21:44:30Z","timestamp":1694123070000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,9]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1111\/epi.16374"],"URL":"https:\/\/doi.org\/10.1111\/epi.16374","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,9]]},"assertion":[{"value":"2019-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}