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% O(2)). 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), S100beta, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous concentration difference (a-v(D)) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P < 0.05 vs. normoxia) that correlated with the increase in AMS/headache scores (r = -0.50 to -0.90, P < 0.05). This was associated with a reduction in a-v(D) and hence net cerebral uptake of plasma nitrite and increased cerebral output of 3-NT (P < 0.05 vs. normoxia) that also correlated against AMS/headache scores (r = 0.74-0.87, P < 0.05). In contrast, hypoxia did not alter the cerebral exchange of S100beta and both global cerebral oxidative metabolism (cerebral metabolic rate of oxygen) and neuronal integrity (NSE) were preserved (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.

The purpose of this study was to compare power outputs, and blood concentrations of lipid hydroperoxides (LH), malondialdehyde (MDA), creatine kinase (CK), myoglobin (Mb) and lactate ([La-]B) following 30 s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Alpha-tocopherol (AT), retinol (R) and uric acid (UA) concentrations were also measured to qualify the activity of antioxidants. Cardiac troponin levels were determined to exclude myocardial damage and to verify that any CK was predominantly derived from skeletal muscle. Differences (P<0.05) in peak power output, pedal velocity and resistive forces were observed when the TBM and FFM protocols were compared [953 (114) W vs 1,020 (134) W; 134 (8) rpm vs 141 (7) rpm; 6 (1) kg vs 5 (1) kg respectively). LH and MDA concentrations increased immediately post-exercise during the TBM protocol only (P<0.05) and were greater when compared to FFM (P<0.05). LH and MDA values decreased 24 h post-exercise. Increases in CK concentrations were recorded immediately post-exercise for both the TBM and FFM protocols with greater concentrations recorded for TBM (P<0.05). Decreases were observed 24 h post-exercise. Mb concentrations were greater immediately post-exercise for the TBM protocol and were greater than those recorded for FFM (P<0.05). Values decreased 24 h later (P<0.05). AT and UA concentrations decreased immediately post-exercise for both protocols (P<0.05) and increased 24 h later (P<0.05). There were no changes observed in R concentrations at any of the blood sampling stages. [La-]B increased (P<0.05) immediately post-exercise for both protocols, and decreased 24 h later (P<0.05). The results of the study suggest that greater power outputs are obtainable with significantly less oxidative stress and muscle disruption when resistive forces reflect FFM mass as opposed to TBM.

The present study examined whether dynamic cerebral autoregulation and blood-brain barrier function would become compromised as a result of exercise-induced oxidative-nitrosative stress. Eight healthy men were examined at rest and after an incremental bout of semi-recumbent cycling exercise to exhaustion. Changes in a dynamic cerebral autoregulation index were determined during recovery from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and mean arterial pressure during transiently induced hypotension. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites in venous blood. Neuron-specific enolase, S100β and 3-nitrotyrosine were determined by ELISA. While exercise did not alter MCAv, it caused a mild reduction in the autoregulation index (from 6.9 ± 0.6 to 5.5 ± 0.9 a.u., P < 0.05) that correlated directly against the exercise-induced increase in the ascorbate radical, 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N -oxide and N -tert-butyl-α-phenylnitrone adducts, 3-nitrotyrosine and S100β (r = -0.66 to -0.76, P < 0.05). In contrast, no changes in neuron-specific enolase were observed. In conclusion, our findings suggest that intense exercise has the potential to increase blood-brain barrier permeability without causing structural brain damage subsequent to a free radical-mediated impairment in dynamic cerebral autoregulation.

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This study confirms significantly higher levels of plasma homocysteine in AAA patients but lower levels of B12. Use of supplemental vitamins that should lower plasma homocysteine may modify vascular disease progression. Clinical trials in this direction are warranted.