{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:03:18Z","timestamp":1792098198543,"version":"4.4.0"},"reference-count":55,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier (BBB) and, subsequently, lead to the development of cerebral edema and the defining symptoms of AMS. This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption. Twenty healthy volunteers participated in a series of hypobaric hypoxia trials distinguished by pretreatment with placebo, acetazolamide (250 mg), or dexamethasone (4 mg), administered using a randomized, double-blind, placebo-controlled, crossover design. Each trial included peripheral blood sampling and AMS assessment before (\u221215 and 0 h) and during (0.5, 4, and 9 h) a 10-h hypoxic exposure (barometric pressure = 425 mmHg). Anti-inflammatory and\/or anti-permeability [interleukin (IL)-1 receptor agonist (IL-1RA), heat shock protein (HSP)-70, and adrenomedullin], proinflammatory (IL-6, IL-8, IL-2, IL-1\u03b2, and substance P), angiogenic, or chemotactic biomarkers (macrophage inflammatory protein-1\u03b2, VEGF, TNF-\u03b1, monocyte chemotactic protein-1, and matrix metalloproteinase-9) were assessed. AMS-resistant subjects had higher IL-1RA (4 and 9 h and overall), HSP-70 (0 h and overall), and adrenomedullin (overall) compared with AMS-susceptible subjects. Acetazolamide raised IL-1RA and HSP-70 compared with placebo in AMS-susceptible subjects. Dexamethasone also increased HSP-70 and adrenomedullin in AMS-susceptible subjects. Macrophage inflammatory protein-1\u03b2 was higher in AMS-susceptible than AMS-resistant subjects after 4 h of hypoxia; dexamethasone minimized this difference. Other biomarkers were unrelated to AMS. Resistance to AMS was accompanied by a marked anti-inflammatory and\/or anti-permeability response that may have prevented downstream pathophysiological events leading to AMS. Conversely, AMS susceptibility does not appear to be related to an exaggerated inflammatory response.<\/jats:p>","DOI":"10.1152\/japplphysiol.00391.2011","type":"journal-article","created":{"date-parts":[[2011,6,4]],"date-time":"2011-06-04T00:18:54Z","timestamp":1307146734000},"page":"392-399","source":"Crossref","is-referenced-by-count":103,"title":["Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study"],"prefix":"10.1152","volume":"111","author":[{"given":"Colleen Glyde","family":"Julian","sequence":"first","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Subudhi","sequence":"additional","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"},{"name":"Department of Biology, University of Colorado, Colorado Springs, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Dimmen","sequence":"additional","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Pecha","sequence":"additional","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Roach","sequence":"additional","affiliation":[{"name":"Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007074420772"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00704.2003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13591-X"},{"key":"B5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1189\/jlb.71.4.603","volume":"71","author":"Coakley RJ","year":"2002","journal-title":"J Leukoc Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.28.17787"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2003.09.079"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2009.09.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00915-8"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/00008506-200401000-00010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385114-7.00007-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450206"},{"key":"B13","first-page":"950","volume":"59","author":"Hackett PH","year":"1988","journal-title":"Aviat Space Environ Med"},{"key":"B14","doi-asserted-by":"crossref","first-page":"779","DOI":"10.33549\/physiolres.931032","volume":"56","author":"Haditsch B","year":"2007","journal-title":"Physiol Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1999.0533"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.2.R513"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-006-9028-x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)02004-X"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.4.7895664"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/325253a0"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600404"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2008.08.010"},{"key":"B23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/978-3-7091-0651-8_115","volume":"86","author":"Kis B","year":"2003","journal-title":"Acta Neurochir Suppl (Wien)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s004210050278"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01572.2005"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-170316"},{"key":"B27","first-page":"300","volume-title":"High Altitude Medicine","author":"Matsuzawa Y","year":"1992"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2005"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1866"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1038"},{"key":"B31","first-page":"1770","volume":"40","author":"Moldow B","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705462"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00061-3"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1104"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1580\/0953-9859-5.1.34"},{"key":"B36","first-page":"272","volume-title":"Hypoxia and Molecular Medicine","author":"Roach RCBP","year":"1993"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.2.581"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-1591(02)00098-3"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600513"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/359843a0"},{"key":"B41","first-page":"411","volume":"51","author":"Sirovskiy E","year":"1990","journal-title":"Acta Neurochir Suppl (Wien)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/3-211-30714-1_91"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600055"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.3.L419"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01393.2010"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.574749"},{"key":"B47","first-page":"499","volume":"68","author":"Swenson ER","year":"1997","journal-title":"Aviat Space Environ Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s007010100007"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199812000-00010"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000327885.15132.CA"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2003.09.004"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2004.15.1243"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.10.027"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1344.007"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-008-0094-5"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.00391.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T06:13:58Z","timestamp":1686118438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.00391.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["10.1152\/japplphysiol.00391.2011"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.00391.2011","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8]]}}}