{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:40:22Z","timestamp":1773308422955,"version":"3.50.1"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2007,5,22]],"date-time":"2007-05-22T00:00:00Z","timestamp":1179792000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"DOI":"10.1371\/journal.pmed.0040173","type":"journal-article","created":{"date-parts":[[2007,5,16]],"date-time":"2007-05-16T13:19:11Z","timestamp":1179321551000},"page":"e173","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":42,"title":["Hyperoxic Brain Effects Are Normalized by Addition of CO2"],"prefix":"10.1371","volume":"4","author":[{"given":"Paul M","family":"Macey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary A","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald M","family":"Harper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2007,5,22]]},"reference":[{"key":"pmed-0040173-b001","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1152\/jappl.1953.5.9.471","article-title":"Oxygen toxicity; effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism.","volume":"5","year":"1953","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b002","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1152\/japplphysiol.00864.2002","article-title":"Hyperbaric oxygen and chemical oxidants stimulate CO2\/H+-sensitive neurons in rat brain stem slices.","volume":"95","year":"2003","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b003","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1152\/jappl.1996.81.4.1683","article-title":"Effect of different levels of hyperoxia on breathing in healthy subjects.","volume":"81","year":"1996","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b004","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1113\/jphysiol.1951.sp004620","article-title":"The effect of inhalation of high and low oxygen concentrations on the respiration of the newborn infant.","volume":"114","year":"1951","journal-title":"J Physiol"},{"key":"pmed-0040173-b005","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1152\/jappl.1998.85.1.129","article-title":"Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat: putative role of nitric oxide.","volume":"85","year":"1998","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b006","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1378\/chest.128.1.430","article-title":"Hyperoxia-induced hypocapnia: An underappreciated risk.","volume":"128","year":"2005","journal-title":"Chest"},{"key":"pmed-0040173-b007","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/S0022-5223(03)01044-4","article-title":"Does hyperoxia affect glucose regulation and transport in the newborn?","volume":"126","year":"2003","journal-title":"J Thorac Cardiovasc Surg"},{"key":"pmed-0040173-b008","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1475-097X.2004.00572.x","article-title":"Hyperoxia-induced arterial compliance decrease in healthy man.","volume":"25","year":"2005","journal-title":"Clin Physiol Funct Imaging"},{"key":"pmed-0040173-b009","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/00005344-200308000-00014","article-title":"Cardiovascular effects of acute oxygen administration in healthy adults.","volume":"42","year":"2003","journal-title":"J Cardiovasc Pharmacol"},{"key":"pmed-0040173-b010","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/00005072-198605000-00005","article-title":"Hyperoxia produces neuronal necrosis in the rat.","volume":"45","year":"1986","journal-title":"J Neuropathol Exp Neurol"},{"key":"pmed-0040173-b011","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF00238548","article-title":"Effect of exposure to oxygen at 101 and 150 kPa on the cerebral circulation and oxygen supply in conscious rats.","volume":"71","year":"1995","journal-title":"Eur J Appl Physiol Occup Physiol"},{"key":"pmed-0040173-b012","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11055-005-0035-z","article-title":"Involvement of interferon-alpha in the regulation of apoptosis of cells of the hypothalamo-hypophyseal-adrenocortical system of aged mice in oxidative stress.","volume":"35","year":"2005","journal-title":"Neurosci Behav Physiol"},{"key":"pmed-0040173-b013","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1469-7793.2000.t01-1-00259.x","article-title":"Cerebral correlates of autonomic cardiovascular arousal: A functional neuroimaging investigation in humans.","volume":"523","year":"2000","journal-title":"J Physiol"},{"key":"pmed-0040173-b014","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1152\/japplphysiol.00881.2002","article-title":"fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects.","volume":"94","year":"2003","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b015","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1152\/jn.00107.2002","article-title":"Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging.","volume":"88","year":"2002","journal-title":"J Neurophysiol"},{"key":"pmed-0040173-b016","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/cne.902570206","article-title":"A role of insular cortex in cardiovascular function.","volume":"257","year":"1987","journal-title":"J Comp Neurol"},{"key":"pmed-0040173-b017","first-page":"R245","article-title":"Subcortical sites mediating sympathetic responses from insular cortex in rats.","volume":"258","year":"1990","journal-title":"Am J Physiol"},{"key":"pmed-0040173-b018","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0006-8993(98)00996-2","article-title":"Insular cortex lesions alter baroreceptor sensitivity in the urethane-anesthetized rat.","volume":"813","year":"1998","journal-title":"Brain Res"},{"key":"pmed-0040173-b019","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.yfrne.2003.07.001","article-title":"Central mechanisms of stress integration: Hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness.","volume":"24","year":"2003","journal-title":"Front Neuroendocrinol"},{"key":"pmed-0040173-b020","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1172\/JCI101995","article-title":"The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men.","volume":"27","year":"1948","journal-title":"J Clin Invest"},{"key":"pmed-0040173-b021","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.resp.2005.05.024","article-title":"Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.","volume":"151","year":"2006","journal-title":"Respir Physiol Neurobiol"},{"key":"pmed-0040173-b022","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation.","volume":"26","year":"2005","journal-title":"Neuroimage"},{"key":"pmed-0040173-b023","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.resp.2003.09.006","article-title":"Global BOLD MRI changes to ventilatory challenges in congenital central hypoventilation syndrome.","volume":"139","year":"2003","journal-title":"Respir Physiol Neurobiol"},{"key":"pmed-0040173-b024","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/mrm.1134","article-title":"MRI mapping of cerebrovascular reactivity using square wave changes in end-tidal PCO2.","volume":"45","year":"2001","journal-title":"Magn Reson Med"},{"key":"pmed-0040173-b025","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.neuroimage.2003.12.042","article-title":"A method for removal of global effects from fMRI time series.","volume":"22","year":"2004","journal-title":"Neuroimage"},{"key":"pmed-0040173-b026","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1006\/nimg.2001.1037","article-title":"Thresholding of statistical maps in functional neuroimaging using the false discovery rate.","volume":"15","year":"2002","journal-title":"Neuroimage"},{"key":"pmed-0040173-b027","unstructured":"CohenJ 1988 Statistical power analysis for the behavioral sciences Hillsdale (New Jersey) Erlbaum 567"},{"key":"pmed-0040173-b028","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1152\/jn.00863.2004","article-title":"Hypercapnic exposure in congenital central hypoventilation syndrome reveals CNS respiratory control mechanisms.","volume":"93","year":"2005","journal-title":"J Neurophysiol"},{"key":"pmed-0040173-b029","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1152\/japplphysiol.00969.2004","article-title":"Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome.","volume":"98","year":"2005","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b030","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1203\/01.PDR.0000155763.93819.46","article-title":"FMRI responses to hyperoxia in congenital central hypoventilation syndrome.","volume":"57","year":"2005","journal-title":"Pediatr Res"},{"key":"pmed-0040173-b031","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1203\/01.PDR.0000125262.82405.3C","article-title":"Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome.","volume":"55","year":"2004","journal-title":"Pediatr Res"},{"key":"pmed-0040173-b032","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1152\/jappl.1995.78.2.696","article-title":"Ventilatory response to isocapnic hyperoxia.","volume":"78","year":"1995","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b033","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1152\/japplphysiol.01185.2005","article-title":"Effects of short-term isocapnic hyperoxia and hypoxia on cardiovascular function.","volume":"101","year":"2006","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b034","first-page":"170","article-title":"CO2 breathing and the ouput of the heart.","volume":"6","year":"1943","journal-title":"Acta Physiol Scand"},{"key":"pmed-0040173-b035","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/cne.903590107","article-title":"Ascending projections of the posterior nucleus of the hypothalamus: PHA-L analysis in the rat.","volume":"359","year":"1995","journal-title":"J Comp Neurol"},{"key":"pmed-0040173-b036","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/BF02281899","article-title":"Left-insular cortex lesions perturb cardiac autonomic tone in humans.","volume":"6","year":"1996","journal-title":"Clin Auton Res"},{"key":"pmed-0040173-b037","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1152\/japplphysiol.00852.2003","article-title":"Functional magnetic resonance signal changes in neural structures to baroreceptor reflex activation.","volume":"96","year":"2004","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b038","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1113\/jphysiol.2005.091637","article-title":"Cortical regions associated with autonomic cardiovascular regulation during lower body negative pressure in humans.","volume":"569","year":"2005","journal-title":"J Physiol"},{"key":"pmed-0040173-b039","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/cne.903030303","article-title":"Autonomic responses and efferent pathways from the insular cortex in the rat.","volume":"303","year":"1991","journal-title":"J Comp Neurol"},{"key":"pmed-0040173-b040","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/japplphysiol.00134.2004","article-title":"Medial vestibular nucleus mediates the cardiorespiratory responses to fastigial nuclear activation and hypercapnia.","volume":"97","year":"2004","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b041","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0006-8993(83)90134-8","article-title":"Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin.","volume":"269","year":"1983","journal-title":"Brain Res"},{"key":"pmed-0040173-b042","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0306-4522(99)00347-4","article-title":"Physiological and ventral medullary surface activity during hypovolemia.","volume":"94","year":"1999","journal-title":"Neuroscience"},{"key":"pmed-0040173-b043","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0165-0173(01)00080-7","article-title":"Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems.","volume":"38","year":"2001","journal-title":"Brain Res Brain Res Rev"},{"key":"pmed-0040173-b044","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0006-8993(82)90974-X","article-title":"Some observations on hypothalamo-amygdaloid connections in the monkey.","volume":"252","year":"1982","journal-title":"Brain Res"},{"key":"pmed-0040173-b045","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/0006-8993(88)90701-9","article-title":"Cardiovascular and respiratory responses to electrical and chemical stimulation of the hippocampus in anesthetized and awake rats.","volume":"457","year":"1988","journal-title":"Brain Res"},{"key":"pmed-0040173-b046","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0306-4522(95)00525-0","article-title":"Hippocampal activity during transient respiratory events in the freely behaving cat.","volume":"72","year":"1996","journal-title":"Neuroscience"},{"key":"pmed-0040173-b047","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0006-8993(90)90177-D","article-title":"Respiratory-related discharge of periaqueductal gray neurons during sleep-waking states.","volume":"511","year":"1990","journal-title":"Brain Res"},{"key":"pmed-0040173-b048","doi-asserted-by":"crossref","first-page":"R1338","DOI":"10.1152\/ajpregu.00828.2004","article-title":"Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation in rats.","volume":"289","year":"2005","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"pmed-0040173-b049","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1152\/japplphysiol.00740.2002","article-title":"Respiratory response to activation or disinhibition of the dorsal periaqueductal gray in rats.","volume":"94","year":"2003","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b050","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1373\/clinchem.2005.061408","article-title":"Biomarkers of oxidative damage in human disease.","volume":"52","year":"2006","journal-title":"Clin Chem"},{"key":"pmed-0040173-b051","unstructured":"FarberJL 1985 The biochemical pathology of toxic cell death. Monogr Pathol 19 31"},{"key":"pmed-0040173-b052","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0169-328X(03)00025-1","article-title":"VEGF-induced activation of the PI3-K\/Akt pathway reduces mutant SOD1-mediated motor neuron cell death.","volume":"111","year":"2003","journal-title":"Brain Res Mol Brain Res"},{"key":"pmed-0040173-b053","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000080950","article-title":"Resuscitation of depressed newborn infants with ambient air or pure oxygen: A meta-analysis.","volume":"87","year":"2005","journal-title":"Biol Neonate"},{"key":"pmed-0040173-b054","doi-asserted-by":"crossref","unstructured":"TanASchulzeAO'DonnellCPDavisPG 2005 Air versus oxygen for resuscitation of infants at birth. Cochrane Database Syst Rev CD002273.","DOI":"10.1002\/14651858.CD002273.pub3"},{"key":"pmed-0040173-b055","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1067\/mpd.2003.91","article-title":"Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen.","volume":"142","year":"2003","journal-title":"J Pediatr"},{"key":"pmed-0040173-b056","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1164\/rccm.200412-1740OC","article-title":"Room-air resuscitation causes less damage to heart and kidney than 100% oxygen.","volume":"172","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"pmed-0040173-b057","doi-asserted-by":"crossref","first-page":"H553","DOI":"10.1152\/ajpheart.00657.2003","article-title":"Hyperoxia causes oxygen free radical-mediated membrane injury and alters myocardial function and hemodynamics in the newborn.","volume":"287","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"pmed-0040173-b058","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/S0140-6736(00)04054-X","article-title":"Hyperbaric oxygen for children with cerebral palsy: A randomised multicentre trial. HBO-CP Research Group.","volume":"357","year":"2001","journal-title":"Lancet"},{"key":"pmed-0040173-b059","doi-asserted-by":"crossref","first-page":"F49","DOI":"10.1136\/adc.2003.048785","article-title":"Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia?","volume":"90","year":"2005","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"pmed-0040173-b060","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1542\/peds.95.6.868","article-title":"Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: An experimental study in the immature rat.","volume":"95","year":"1995","journal-title":"Pediatrics"},{"key":"pmed-0040173-b061","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1152\/jappl.1994.76.5.2076","article-title":"Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging.","volume":"76","year":"1994","journal-title":"J Appl Physiol"},{"key":"pmed-0040173-b062","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.neuroimage.2005.04.036","article-title":"The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation.","volume":"27","year":"2005","journal-title":"Neuroimage"},{"key":"pmed-0040173-b063","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.neuroimage.2004.12.010","article-title":"Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals.","volume":"25","year":"2005","journal-title":"Neuroimage"},{"key":"pmed-0040173-b064","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1006\/nimg.2001.0760","article-title":"Does hypercapnia-induced cerebral vasodilation modulate the hemodynamic response to neural activation?","volume":"13","year":"2001","journal-title":"Neuroimage"}],"container-title":["PLoS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.0040173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T09:23:54Z","timestamp":1707902634000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.0040173"}},"subtitle":[],"editor":[{"given":"Mervyn","family":"Singer","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2007,5,22]]},"references-count":64,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2007,5,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.0040173","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,22]]}}}