{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:03:07Z","timestamp":1777366987528,"version":"3.51.4"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ibroneuroscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.neuroscience.2019.09.025","type":"journal-article","created":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T05:19:57Z","timestamp":1572671997000},"page":"32-43","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Caffeine Exacerbates Postictal Hypoxia"],"prefix":"10.1016","volume":"422","author":[{"given":"Thomas J.","family":"Phillips","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renaud C.","family":"Gom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marshal D.","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Campbell","family":"Teskey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2019.09.025_b0005","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1002\/hbm.20732","article-title":"The effect of daily caffeine use on cerebral blood flow: how much caffeine can we tolerate?","volume":"30","author":"Addicott","year":"2009","journal-title":"Human Brain Map"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0010","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/caff.2017.0011","article-title":"Kinetic and dynamic description of caffeine","volume":"8","author":"Alsabri","year":"2018","journal-title":"J Caff Adenosine Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0015","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11910-019-0948-5","article-title":"The use of caffeine by people with epilepsy: the myths and the evidence","volume":"19","author":"Bauer","year":"2019","journal-title":"Curr Neurol Neurosci Rep"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0020","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.coph.2007.09.002","article-title":"Adenosine as a neuromodulator in neurological diseases","volume":"8","author":"Boison","year":"2008","journal-title":"Curr Opin Pharmacol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0025","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3109\/03602538409029964","article-title":"Interspecies comparison of in vivo caffeine pharmacokinetics in man, monkey, rabbit, rat and mouse","volume":"15","author":"Bonati","year":"1984","journal-title":"Drug Metabol Rev"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0030","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1161\/CIRCRESAHA.116.309726","article-title":"Purinergic signaling in the cardiovascular system","volume":"120","author":"Burnstock","year":"2017","journal-title":"Circul Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0035","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2174\/0929867320666131119152201","article-title":"Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic?","volume":"21","author":"Curia","year":"2014","journal-title":"Curr Med Chem"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0040","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1021\/jm00345a001","article-title":"Adenosine receptors: targets for future drugs","volume":"25","author":"Daly","year":"1982","journal-title":"J Med Chem"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0045","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1528-1157.1985.tb05684.x","article-title":"Is adenosine an endogenous anticonvulsant?","volume":"26","author":"Dragunow","year":"1985","journal-title":"Epilepsia"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0050","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ana.410320504","article-title":"Adenosine: a potential mediator of seizure arrest and postictal refractoriness","volume":"32","author":"During","year":"1992","journal-title":"Annal Neurol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0055","article-title":"Caffeine's vascular mechanisms of action","volume":"2010","author":"Echeverri","year":"2010","journal-title":"Intern J Vasc Med"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0060","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.eplepsyres.2016.05.007","article-title":"Susceptibility to seizure-induced sudden death in DBA\/2 mice is altered by adenosine","volume":"124","author":"Faingold","year":"2016","journal-title":"Epilepsy Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0065","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0306-4522(87)92961-7","article-title":"The distribution of adenosine A1 receptors and 5'-nucleotidase in the brain of some commonly used experimental animals","volume":"22","author":"Fastbom","year":"1987","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0070","first-page":"S553","article-title":"Tissue PO2 threshold of ischemic cell damage following MCA occlusion in cats","volume":"11","author":"Farrar","year":"1991","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0075","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1111\/epi.13827","article-title":"Postictal hypoperfusion\/hypoxia provides the foundation for a unified theory of seizure-induced brain abnormalities and behavioral dysfunction","volume":"58","author":"Farrell","year":"2017","journal-title":"Epilepsia"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0080","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.19352","article-title":"Postictal behavioural impairments are due to a severe prolonged hypoperfusion\/hypoxia event that is COX-2 dependent","volume":"5","author":"Farrell","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0085","doi-asserted-by":"crossref","first-page":"17935","DOI":"10.1038\/s41598-018-36287-2","article-title":"Fast oxygen dynamics as a potential biomarker for epilepsy","volume":"8","author":"Farrell","year":"2018","journal-title":"Sci Rep"},{"issue":"2","key":"10.1016\/j.neuroscience.2019.09.025_b0090","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.0954-6820.1985.tb01650.x","article-title":"On the mechanism of action of theophylline and caffeine","volume":"217","author":"Fredholm","year":"1985","journal-title":"Acta Med Scand"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0095","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0031-6997(24)01396-6","article-title":"Actions of caffeine in the brain with special reference to factors that contribute to its widespread use","volume":"51","author":"Fredholm","year":"1999","journal-title":"Pharmacol Revs"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0100","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1093\/brain\/awx241","article-title":"Seizure onset zone localization using postictal hypoperfusion detected by arterial spin labelling MRI","volume":"140","author":"Gaxiola-Valdez","year":"2017","journal-title":"Brain"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0105","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1523\/JNEUROSCI.02-09-01230.1982","article-title":"Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine","volume":"2","author":"Goodman","year":"1982","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0110","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12017-012-8203-0","article-title":"Hypoxia markers are expressed in interneurons exposed to recurrent seizures","volume":"15","author":"Gualtieri","year":"2013","journal-title":"Neuromol Med"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0115","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1007\/BF00370755","article-title":"The action of caffeine on inward barium current through voltage-dependent calcium channels in single rabbit ear artery cells","volume":"416","author":"Hughes","year":"1990","journal-title":"Pflugers Archiv: Euro J Physiol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0120","doi-asserted-by":"crossref","first-page":"C1172","DOI":"10.1152\/ajpcell.1996.271.4.C1172","article-title":"Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension","volume":"271","author":"Jiang","year":"1996","journal-title":"Am J Physiol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0125","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1212\/WNL.0000000000002398","article-title":"An investigation into the psychosocial effects of the postictal state","volume":"86","author":"Josephson","year":"2016","journal-title":"Neurology"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0130","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0006-8993(84)90694-2","article-title":"The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant","volume":"321","author":"Lee","year":"1984","journal-title":"Brain Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0135","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00234-019-02227-8","article-title":"CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread","volume":"61","author":"Li","year":"2019","journal-title":"Neuroradiology"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0145","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yebeh.2015.04.003","article-title":"Ischemic-hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus","volume":"49","author":"Lucchi","year":"2015","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0150","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.expneurol.2011.12.026","article-title":"Caffeine prevents acute mortality after TBI in rats without increased morbidity","volume":"234","author":"Lusardi","year":"2012","journal-title":"Exp Neurol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0155","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.pediatrneurol.2017.03.002","article-title":"Most children with epilepsy experience postictal phenomena, often preventing a return to normal activities of childhood","volume":"72","author":"MacEachern","year":"2017","journal-title":"Ped Neurol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0160","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1097\/CCM.0b013e3181a009f8","article-title":"Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review","volume":"37","author":"Maloney-Wilensky","year":"2009","journal-title":"Crit Care Med"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0165","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0896-6273(91)90070-G","article-title":"The brain ryanodine receptor: a caffeine-sensitive calcium release channel","volume":"7","author":"McPherson","year":"1991","journal-title":"Neuron"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0170","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.fct.2013.10.042","article-title":"Beverage caffeine intakes in the US","volume":"63","author":"Mitchell","year":"2014","journal-title":"Food Chem Toxicol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0175","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12028-008-9133-4","article-title":"Dantrolene: mechanisms of neuroprotection and possible clinical applications in the neurointensive care unit","volume":"10","author":"Muehlschlegel","year":"2009","journal-title":"Neurocrit Care"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0180","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1006\/nimg.2001.0973","article-title":"On the use of caffeine as a contrast booster for BOLD fMRI studies","volume":"15","author":"Mulderink","year":"2002","journal-title":"Neuroimage"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0185","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.4049\/jimmunol.179.11.7431","article-title":"1, 3, 7-trimethylxanthine (caffeine) may exacerbate acute inflammatory liver injury by weakening the physiological immunosuppressive mechanism","volume":"179","author":"Ohta","year":"2007","journal-title":"J Immunol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0190","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jneumeth.2010.08.019","article-title":"A method for measuring brain partial pressure of oxygen in unanesthetized unrestrained subjects: the effect of acute and chronic hypoxia on brain tissue PO2","volume":"193","author":"Ortiz-Prado","year":"2010","journal-title":"J Neurosci Meth"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0200","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0205","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0006-8993(03)03247-5","article-title":"Subcellular localization of adenosine A1 receptors in nerve terminals and synapses of the rat hippocampus","volume":"987","author":"Rebola","year":"2003","journal-title":"Brain Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0210","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drugalcdep.2008.08.001","article-title":"Caffeinated energy drinks\u2014a growing problem","volume":"99","author":"Reissig","year":"2009","journal-title":"Drug Alcoh Depend"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0215","unstructured":"Russell, W.M.S., Burch, R.L, Hume, C.W., 1959. The principles of humane experimental technique (Vol. 238). London: Methuen."},{"key":"10.1016\/j.neuroscience.2019.09.025_b0220","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1111\/bph.12685","article-title":"Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor","volume":"171","author":"Saleem","year":"2014","journal-title":"Brit J Pharmacol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0230","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.yebeh.2019.03.014","article-title":"Signs and symptoms of the post-ictal state in epilepsy: a Systematic review and meta-analysis","volume":"94","author":"Subota","year":"2019","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0235","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.seizure.2009.04.002","article-title":"Postnatal caffeine treatment affects differently two pentylenetetrazol seizure models in rats","volume":"18","author":"Tchekalarova","year":"2009","journal-title":"Seizure"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0240","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.brainres.2010.07.107","article-title":"Postnatal period of caffeine treatment and time of testing modulate the effect of acute caffeine on cortical epileptic afterdischarges in rats","volume":"1356","author":"Tchekalarova","year":"2010","journal-title":"Brain Res"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0245","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/147238","article-title":"Pharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjects","volume":"2013","author":"Teekachunhatean","year":"2013","journal-title":"ISRN Pharmacol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0250","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0006-2952(93)90168-V","article-title":"Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes","volume":"45","author":"Ukena","year":"1993","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0255","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/j.amjcard.2006.06.058","article-title":"Effects of acute administration of caffeine on vascular function","volume":"98","author":"Umemura","year":"2006","journal-title":"Am J Cardiol"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0260","first-page":"868","article-title":"Brain oxygen tension in severe head injury","volume":"46","author":"Van den Brink","year":"2000","journal-title":"Neurosurgery"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0265","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.yebeh.2017.11.003","article-title":"Caffeine and seizures: a systematic review and quantitative analysis","volume":"80","author":"van Koert","year":"2018","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0270","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.3181\/00379727-128-33183","article-title":"The effect of in vitro and in vivo caffeine, theophylline, and hydrocortisone on the phosphodiesterase activity of the pituitary, median eminence, heart, and cerebral cortex of the rat","volume":"128","author":"Vernikos-Danellis","year":"1968","journal-title":"Proceed Soc Exper Biol Med"},{"key":"10.1016\/j.neuroscience.2019.09.025_b0275","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00210-007-0135-0","article-title":"Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A 2A receptor antagonists","volume":"375","author":"Yang","year":"2007","journal-title":"Naunyn-Schmiedeberg's Arch Pharmacol"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219306700?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219306700?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T15:52:36Z","timestamp":1759679556000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306452219306700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":52,"alternative-id":["S0306452219306700"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2019.09.025","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Caffeine Exacerbates Postictal Hypoxia","name":"articletitle","label":"Article Title"},{"value":"Neuroscience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuroscience.2019.09.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 IBRO. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}