{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:14:24Z","timestamp":1790046864913,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"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. Physiol."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent. VEGF level changes with dexamethasone, a commonly used AMS medication, may provide additional insight into AMS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Twelve healthy volunteers ascended Mt Fuji (3,700 m) and blood samples were obtained at distinct altitudes for VEGF analysis. Oxygen saturation (SPO2) measurements were also documented at the same time-point. Six out of the 12 study participants were prescribed dexamethasone for a second ascent performed 48 h later, and blood was again collected to establish VEGF levels.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Four key VEGF observations could be made based on the data collected: (i) the baseline VEGF levels between the two ascents trended upwards; (ii) those deemed to have AMS in the first ascent had increased VEGF levels (23.8\u201330.3 pg\/ml), which decreased otherwise (23.8\u201330.3 pg\/ml); (iii) first ascent AMS participants had higher VEGF level variability for the second ascent, and similar to those not treated with dexamethasone; and (iv) for the second ascent dexamethasone participants had similar VEGF levels to non-AMS first ascent participants, and the variability was lower than for first ascent AMS and non-dexamethasone participants. SPO2 changes were unremarkable, other than reducing by around 5% irrespective of whether measurement was taken for the first or second ascent.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> First ascent findings suggest a hallmark of AMS could be elevated VEGF levels. The lack of an exercise-induced VEGF level change strengthened the notion that elevated plasma VEGF was brain-derived, and related to AMS.<\/jats:p>","DOI":"10.3389\/fphys.2021.746044","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T07:20:39Z","timestamp":1634800839000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure"],"prefix":"10.3389","volume":"12","author":[{"given":"Craig","family":"Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Bjorkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cardinal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"O\u2019Rourke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Ballard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Nasrallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Vegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/sj.embor.7400598","article-title":"The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling.","volume":"7","author":"Berra","year":"2006","journal-title":"EMBO Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1159\/000322850","article-title":"Polymorphisms of hypoxia-related genes in subjects susceptible to acute mountain sickness.","volume":"81","author":"Ding","year":"2011","journal-title":"Respiration"},{"key":"B3","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.rmed.2006.06.014","article-title":"Change in plasma vascular endothelial growth factor during onset and recovery from acute mountain sickness.","volume":"101","author":"Dorward","year":"2007","journal-title":"Respir. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2010.02.029","article-title":"Hypoxic preconditioning provides neuroprotection and increases vascular endothelial growth factor a, preserves the phosphorylation of Akt-Ser-473 and diminishes the increase in caspase-3 activity in neonatal rat hypoxic-ischaemic model.","volume":"1325","author":"Feng","year":"2010","journal-title":"Brain Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.neuroscience.2011.01.050","article-title":"Dexamethasone pre-treatment protects brain against hypoxic-ischaemic injury partially through up-regulation of vascular endothelial growth factor A in neonatal rates.","volume":"179","author":"Feng","year":"2011","journal-title":"Neuroscience"},{"key":"B6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/S0014-2999(00)00915-8","article-title":"In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor.","volume":"411","author":"Fischer","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","article-title":"Activation of vascular endothelial factor gene transcription by hypoxia-inducible factor 1.","volume":"16","author":"Forsyth","year":"1996","journal-title":"Mol. Cell Biol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110774","article-title":"The effects of cold exposure on leukocytes, hormones and cytokines during acute exercise in humans.","volume":"9","author":"Gagnon","year":"2014","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1073\/pnas.0705680105","article-title":"PHDs overactivation during chronic hypoxia \u2018desensitizes\u2019 HIF alpha and protects cells from necrosis.","volume":"105","author":"Ginouves","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neulet.2008.12.047","article-title":"The molecular mechanism of dexamethasone-mediated effect on blood-brain barrier permeability in a rat brain tumor model.","volume":"452","author":"Gu","year":"2009","journal-title":"Neurosci. Lett."},{"key":"B11","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1056\/NEJM200107123450206","article-title":"High-altitude illness.","volume":"345","author":"Hackett","year":"2001","journal-title":"N. Eng. J. Med."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057374","article-title":"Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.","volume":"8","author":"Hegeman","year":"2013","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.pcad.2010.02.003","article-title":"Acute mountain sickness: pathophysiology, prevention, and treatment.","volume":"52","author":"Imray","year":"2010","journal-title":"Prog. Cardiovasc. Dis."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086407","article-title":"Vascular endothelial growth factors enhance the permeability of the mouse blood-brain barrier.","volume":"9","author":"Jiang","year":"2014","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s12013-012-9374-x","article-title":"A study of high-altitude hypoxia-induced cell stress in murine model.","volume":"64","author":"Juan","year":"2012","journal-title":"Cell Biochem. Biophys."},{"key":"B16","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1152\/japplphysiol.00391.2011","article-title":"Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study.","volume":"111","author":"Julian","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.bbrc.2008.05.025","article-title":"Dexamethasone co-ordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier.","volume":"372","author":"Kim","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3390\/brainsci5020165","article-title":"Growth factors for the treatment of ischemic brain injury (growth factor treatment).","volume":"5","author":"Larpthaveesarp","year":"2015","journal-title":"Brain Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/jnc.12611","article-title":"Ischemic neurons activate astrocytes to disrupt endothelial barrier via increasing VEGF expression.","volume":"129","author":"Li","year":"2014","journal-title":"J. Neurochem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1006\/bbrc.2002.6551","article-title":"Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1.","volume":"291","author":"Liu","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/JOM.0b013e318206b112","article-title":"The Genetics of Altitude Tolerance: the evidence for inherited susceptibility to Acute Mountain Sickness.","volume":"53","author":"MacInnis","year":"2011","journal-title":"J. Occ. Environ. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1378\/chest.118.1.47","article-title":"Plasma vascular endothelial growth factor in acute mountain sickness.","volume":"118","author":"Maloney","year":"2000","journal-title":"Chest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.4103\/0974-2700.44675","article-title":"Vascular endothelial growth factor and acute mountain sickness.","volume":"2","author":"Nilles","year":"2009","journal-title":"J. Emerg. Trauma Shock."},{"key":"B24","doi-asserted-by":"publisher","first-page":"E434","DOI":"10.1152\/ajpendo.00508.2004","article-title":"Acute hypoxia decreases plasma VEGF concentration in healthy humans.","volume":"290","author":"Oltmanns","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1580\/1080-6032(2006)17[1:CDAVEG]2.0.CO;2","article-title":"Cerebrovascular dynamics and vascular endothelial growth factor in acute mountain sickness.","volume":"17","author":"Palma","year":"2006","journal-title":"Wilderness Environ. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/j.1748-1716.2008.01915.x","article-title":"Angiogenic\/lymphangiogenic factors and adaptation to extreme altitudes during an expedition to Mount Everest.","volume":"196","author":"Patitucci","year":"2009","journal-title":"Acta Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1089\/15270290260131920","article-title":"Ventilatory changes during intermittent hypoxia: importance of pattern and duration.","volume":"1","author":"Prabhakar","year":"2002","journal-title":"High Alt. Med. Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.ijdevneu.2011.06.003","article-title":"Impaired hypoxic response in senescent mouse brain.","volume":"29","author":"Rabie","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"B29","first-page":"272","article-title":"The Lake Louise acute mountain sickness scoring system","author":"Roach","year":"1993","journal-title":"Hypoxia and Molecular Medicine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1249\/MSS.0b013e3182a142da","article-title":"Resistance exercise increases endothelial progenitor cells and angiogenic factors.","volume":"46","author":"Ross","year":"2014","journal-title":"Med. Sci. Sports Exerc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"H179","DOI":"10.1152\/ajpheart.00828.2009","article-title":"Maternal glucocorticoid exposure alters tight junction protein expressin in the brain of fetal sheep.","volume":"298","author":"Sadowski","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1093\/brain\/awf257","article-title":"Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain.","volume":"125","author":"Schoch","year":"2002","journal-title":"Brain"},{"key":"B33","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1089\/ham.2011.1020","article-title":"No correlation between plasma levels of vascular endothelial growth factor or its soluble receptor and acute mountain sickness.","volume":"12","author":"Schommer","year":"2011","journal-title":"High Alt. Med. Biol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1042\/AN20100029","article-title":"Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties.","volume":"26","author":"Sen","year":"2011","journal-title":"ASN Neuro."},{"key":"B35","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/s12264-012-1222-x","article-title":"Hypoxic preconditioning in an autohypoxic animal model.","volume":"28","author":"Shao","year":"2012","journal-title":"Neurosci. Bull."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3751","DOI":"10.1038\/sj.onc.1204500","article-title":"Regulation of endothelial growth factor expression by acidosis in human cancer cells.","volume":"20","author":"Shi","year":"2001","journal-title":"Oncogene"},{"key":"B37","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ijcard.2014.03.019","article-title":"Dexamethasone for the prevention of acute mountain sickness: systematic review and meta-analysis.","volume":"173","author":"Tang","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1152\/japplphysiol.00589.2004","article-title":"Greater free plasma VEGF and lower soluble VEGF receptor-1 in acute mountain sickness.","volume":"98","author":"Tissot van Patot","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.archger.2014.04.011","article-title":"Physical exercise and vascular endothelial growth factor (VEGF) in elderly: a systematic review.","volume":"59","author":"Vital","year":"2014","journal-title":"Arch. Gerontol. Geriatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.bbrc.2008.05.061","article-title":"Dexamethasone impairs hypoxia-inducible factor-1 function.","volume":"372","author":"Wagner","year":"2008","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"B41","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1055\/s-0032-1314815","article-title":"Responses of angiogenic growth factors to exercise, to hypoxia and to exercise under hypoxic conditions.","volume":"34","author":"Wahl","year":"2013","journal-title":"Int. J. Sports Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s00421-010-1767-1","article-title":"Effects of acid-base balance and high and low intensity exercise on VEGF and bFGF.","volume":"111","author":"Wahl","year":"2011","journal-title":"Eur. J. Appl. Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s004210100419","article-title":"Effects of high-altitude exposure on vascular endothelial growth factor levels in man.","volume":"85","author":"Walter","year":"2001","journal-title":"Eur. J. Appl. Physiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S1474-4422(09)70014-6","article-title":"The cerebral effects of ascent to high altitudes.","volume":"8","author":"Wilson","year":"2009","journal-title":"Lancet Neurol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s10072-016-2521-1","article-title":"Re-exposure to the hypobaric hypoxic brain injury of high altitude: plasma S100B levels and the possible effect of acclimatisation on blood-brain barrier dysfunction.","volume":"37","author":"Winter","year":"2016","journal-title":"Neurol. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1124\/mol.107.036418","article-title":"Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression.","volume":"72","author":"Yeh","year":"2007","journal-title":"Mol. Pharmacol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.746044\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T07:20:42Z","timestamp":1634800842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.746044\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,21]]},"references-count":46,"alternative-id":["10.3389\/fphys.2021.746044"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.746044","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,21]]},"article-number":"746044"}}