Ascorbate decreases Fabry cerebral hyperperfusion suggesting a reactive oxygen species abnormality: an arterial spin tagging study.
OBJECTIVE
To test the hypothesis that reactive oxygen species contribute to the cerebral hyperperfusion in Fabry disease.


METHODS
We examined the effect of intravenous injection of ascorbate on cerebral blood flow (CBF) using magnetic resonance arterial spin tagging. Nineteen patients with Fabry disease and 15 control subjects were studied as part of a randomized double-blind placebo-controlled trial of enzyme replacement therapy (ERT).


RESULTS
Vertebro-basilar hyperperfusion was observed in patients with Fabry disease. A decrease in systemic ascorbate levels relative to healthy controls was found in the patients. CBF decreased after ascorbate infusion in both control subjects and patients treated with ERT. The placebo group had a significantly delayed decrease in the CBF response after ascorbate infusion. Myeloperoxidase levels were elevated in Fabry patients, consistent with ongoing inflammatory processes in these patients.


CONCLUSIONS
Increased CBF in Fabry disease may be related to increased production of reactive oxygen species, while low plasma ascorbate levels suggests a global redox imbalance. These abnormalities were improved by ERT. These observations have implications regarding oxidative processes contributing to accelerated atherosclerosis in Fabry disease.
Moore
David F
DF
Section of Neurology, Department of Internal Medicine, University of Manitoba, Canada.
Ye
Frank
F
Brennan
Marie-Luise
ML
Gupta
Surya
S
Barshop
Bruce A
BA
Steiner
Robert D
RD
Rhead
William J
WJ
Brady
Roscoe O
RO
Hazen
Stanley L
SL
Schiffmann
Raphael
R
D000328:Adult; D000704:Analysis of Variance; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D000795:Fabry Disease / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017382:Reactive Oxygen Species; D013113:Spin Labels
D017382:Reactive Oxygen Species; D013113:Spin Labels; D001205:Ascorbic Acid