Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

Kevin Evans, Damian Bailey, Sarah Taudorf, Ronan M G Berg, Carsten Lundby, Jane McEneny, Ian S Young, Philip E James, Angharad Shore, David A. Hullin, Joe M McCord, Bente K Pedersen, Kirsten Moller

Research output: Contribution to journalArticlepeer-review


This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein and radial artery blood samples during normoxia and 9-h passive exposure to hypoxia (12.9% O2). Cerebral blood flow was determined by the Kety-Schmidt technique with net exchange calculated by the Fick principle. AMS and headache were determined with clinically validated questionnaires. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites. Neuron-specific enolase (NSE), S100ß, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous concentration difference (a-vD) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P 0.05 vs. normoxia). These findings indicate that hypoxia stimulates cerebral oxidative-nitrative stress, which has broader implications for other clinical models of human disease characterized by hypoxemia. This may prove a risk factor for AMS by a mechanism that appears independent of impaired BBB function and cerebral oxidative metabolism.
Original languageEnglish
Pages (from-to)1283 - 1292
Number of pages9
JournalAmerican Journal of Physiology Regulatory Integrative and Comparative Physiology
Publication statusPublished - 2 Sept 2009


  • blood-brain barrier
  • nitric oxide
  • vasogenic edema
  • electron paramagnetic resonance spectroscopy
  • spin trapping


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