{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T07:08:25Z","timestamp":1793776105912,"version":"4.6.1"},"reference-count":71,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["095064"],"award-info":[{"award-number":["095064"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["200893"],"award-info":[{"award-number":["200893"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:p>\n                    A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in Po\n                    <jats:sub>2<\/jats:sub>\n                    of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation\/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brain stem contains functional oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input.\n                  <\/jats:p>","DOI":"10.1152\/japplphysiol.00194.2017","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T20:10:26Z","timestamp":1495138226000},"page":"1344-1349","source":"Crossref","is-referenced-by-count":102,"title":["On the existence of a central respiratory oxygen sensor"],"prefix":"10.1152","volume":"123","author":[{"given":"Alexander V.","family":"Gourine","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology &amp; Pharmacology, University College London, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Funk","sequence":"additional","affiliation":[{"name":"Department of Physiology, Women and Children\u2019s Health Research Institute, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0045-15.2015"},{"key":"B2","first-page":"964","volume":"49","author":"Bisgard GE","year":"1980","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1976.40.2.184"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(01)00271-7"},{"key":"B5","first-page":"40","volume":"51","author":"Bowes G","year":"1981","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature15721"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01298.2006"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209454200"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.5.1840"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90325.2008"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040239"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.4.1254"},{"key":"B13","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1152\/ajplegacy.1947.148.2.406","volume":"148","author":"Davenport HW","year":"1947","journal-title":"Am J Physiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.079"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1968-11.2011"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.042259"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.01.011"},{"key":"B18","first-page":"769","volume":"49","author":"Gautier H","year":"1980","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1272"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.095968"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.045294"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190721"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3763-04.2005"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1673-5374.2012.14.005"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1965.sp007767"},{"key":"B26","first-page":"632","volume":"46","author":"Honda Y","year":"1979","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.192088"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167861"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6027-09.2010"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2660-09.2009"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.158"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2813-12.2013"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2114\/jpa.17.131"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100069"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3948-06.2007"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.143024"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197111112852002"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04683"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0317-x"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016272"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26309"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(75)90069-9"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00127-4"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1634"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00831.2003"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.64.2.666"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.023"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.247759"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.571bt.x"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.5.1907"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00208.x"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-4584-1_12"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(80)90054-8"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.093328"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00932.2004"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.5.2854"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1992.262.2.R182"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1994.266.1.R245"},{"key":"B59","first-page":"871","volume":"45","author":"Swanson GD","year":"1978","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2009"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05858.2000"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200303000-00026"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.052415"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1113\/JP270369"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1281-16.2016"},{"key":"B66","first-page":"165s","volume":"23","author":"Vermeire P","year":"1987","journal-title":"Bull Eur Physiopathol Respir"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-9048(03)00048-X"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3787-14.2015"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.3.656"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.210930"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.024"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.00194.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:29:44Z","timestamp":1567978184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.00194.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,1]]},"references-count":71,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,11,1]]}},"alternative-id":["10.1152\/japplphysiol.00194.2017"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.00194.2017","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727622592.793532383","asserted-by":"object"}]},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,1]]}}}