1. ¹Department of Physiology, University of Glamorgan, Pontypridd, UK
2. ²Division of Sports Medicine, University of Heidelberg, Heidelberg, Germany
3. ³Department of Neuroradiology, University of Göttingen, Göttingen, Germany
4. ⁴Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany
5. ⁵Centre for Clinical and Population Sciences, Queen's University Belfast, Belfast, UK

Correspondence: Professor DM Bailey, Department of Physiology, University of Glamorgan, Pontypridd, Mid-Glamorgan, South Wales CF37 1DL, UK. E-mail: dbailey1@glam.ac.uk

Received 2 April 2005; Revised 5 May 2005; Accepted 10 May 2005; Published online 15 June 2005.

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 (7.04.8 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.