Exercise-induced oxidative-nitrosative stress is associated with impaired dynamic cerebral autoregulation and blood-brain barrier leakage

David A. Hullin, Kevin Evans, Jane McEneny, Damian Bailey, Ian S. Young, Philip E. James, Shigehiko Ogoh, Philip Ainslie, Céline Luccesi, Antal Rockenbauer, Marcel Culcasi, Sylvia Pietri

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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 restand 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, S100 β 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 andlt;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 S100 β (r =-0.66 to -0.76, P andlt;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.
Original languageEnglish
Pages (from-to)1196 - 1207
Number of pages11
JournalExperimental Physiology
Issue number11
Publication statusPublished - 12 Aug 2011


  • dynamic cerebral autoregulation
  • blood-brain barrier
  • exercise-induced
  • oxidative-nitrosative stress


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