title: Exercise-induced oxidative-nitrosative stress is associated with impaired dynamic cerebral autoregulation and blood-brain barrier leakage.
abstract: 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.
authors.affiliation: Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, Mid-Glamorgan, SouthWales, UK. dbailey1@glam.ac.uk
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Evans
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: David A
authors.initials: DA
authors.lastname: Hullin
authors.forename: Philip E
authors.initials: PE
authors.lastname: James
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Ogoh
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
authors.forename: Céline
authors.initials: C
authors.lastname: Lucchesi
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.forename: Marcel
authors.initials: M
authors.lastname: Culcasi
authors.forename: Sylvia
authors.initials: S
authors.lastname: Pietri
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001812:Blood-Brain Barrier / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004578:Electron Spin Resonance Spectroscopy; D015444:Exercise / Q000502:physiology*; D005609:Free Radicals / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology; D010539:Permeability; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011758:Pyrroles; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: C510912:(diethoxyphosphoryl)-5-methylpyrroline N-oxide; D005609:Free Radicals; D009414:Nerve Growth Factors; D011758:Pyrroles; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D010751:Phosphopyruvate Hydratase