TY - JOUR
T1 - Free radical-mediated damage to barrier function is not associated with altered brain morphology in high-altitude headache
AU - Bailey, Damian
AU - Roukens, Robin
AU - Knauth, Michael
AU - Kallenberg, Kai
AU - Christ, Stefan
AU - Mohr, Alex
AU - Genius, Just
AU - Steiner, Thorstein
AU - Hess, Klaus
AU - Bartsch, Peter
AU - Storch-Hagenlocher, Birgitte
AU - Meisel, Fabian
AU - McEneny, Jane
AU - Young, Ian S
PY - 2005/5/10
Y1 - 2005/5/10
N2 - 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 (Pandlt;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%, Pandlt;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 (Pandlt;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.
AB - 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 (Pandlt;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%, Pandlt;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 (Pandlt;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.
KW - acute mountain sickness
KW - blood–csf barrier
KW - free radicals
KW - headache
KW - vasogenic edema
U2 - 10.1038/sj.jcbfm.9600169
DO - 10.1038/sj.jcbfm.9600169
M3 - Article
C2 - 15959459
SN - 0271-678X
VL - 26
SP - 99
EP - 111
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
ER -