title: Free radical-mediated damage to barrier function is not associated with altered brain morphology in high-altitude headache.
abstract: The present study combined molecular and neuroimaging techniques to examine if free radical-mediated damage to barrier function in hypoxia would result in extracellular edema, raise intracranial pressure (ICP) and account for the neurological symptoms typical of high-altitude headache (HAH) also known as acute mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to 12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h, 8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic resonance (EPR) spectroscopy identified a clear increase in the blood and CSF concentration of O2 and carbon-centered free radicals (P<0.05 versus normoxia) subsequently identified as lipid-derived alkoxyl (LO*) and alkyl (LC*) species. Magnetic resonance imaging (MRI) demonstrated a mild increase in brain volume (7.0+/-4.8 mL or 0.6%+/-0.4%, P<0.05 versus normoxia) that resolved within 6 h of normoxic recovery. However, there was no detectable evidence for gross barrier dysfunction, elevated lumbar pressures, T2 prolongation or associated neuronal and astroglial damage. Clinical AMS was diagnosed in 50% of subjects during the hypoxic trial and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). A greater increase in brain volume was observed, though this was slight, independent of oxidative stress, barrier dysfunction, raised lumbar pressure, vascular damage and measurable evidence of cerebral edema and only apparent in the most severe of cases. These findings suggest that free-radical-mediated vasogenic edema is not an important pathophysiological event that contributes to the mild brain swelling observed in HAH.
authors.affiliation: Department of Physiology, University of Glamorgan, Pontypridd, UK. dbailey1@glam.ac.uk
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.forename: Robin
authors.initials: R
authors.lastname: Roukens
authors.forename: Michael
authors.initials: M
authors.lastname: Knauth
authors.forename: Kai
authors.initials: K
authors.lastname: Kallenberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Christ
authors.forename: Alex
authors.initials: A
authors.lastname: Mohr
authors.forename: Just
authors.initials: J
authors.lastname: Genius
authors.forename: Birgitte
authors.initials: B
authors.lastname: Storch-Hagenlocher
authors.forename: Fabien
authors.initials: F
authors.lastname: Meisel
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Thorsten
authors.initials: T
authors.lastname: Steiner
authors.forename: Klaus
authors.initials: K
authors.lastname: Hess
authors.forename: Peter
authors.initials: P
authors.lastname: Bärtsch
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D001273:Atmosphere Exposure Chambers; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006261:Headache / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D005609:Free Radicals; D010100:Oxygen