Faculty Collaboration Database

Ascorbate decreases Fabry cerebral hyperperfusion suggesting a reactive oxygen species abnormality: an arterial spin tagging study. J Magn Reson Imaging 2004 Oct;20(4):674-83

Date

09/25/2004

Pubmed ID

15390234

DOI

10.1002/jmri.20162

Scopus ID

2-s2.0-4744344117 (requires institutional sign-in at Scopus site)   68 Citations

Abstract

PURPOSE: To test the hypothesis that reactive oxygen species contribute to the cerebral hyperperfusion in Fabry disease.

MATERIAL AND 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.

CONCLUSION: 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.

Author List

Moore DF, Ye F, Brennan ML, Gupta S, Barshop BA, Steiner RD, Rhead WJ, Brady RO, Hazen SL, Schiffmann R

Author

William Rhead MD, PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Analysis of Variance
Ascorbic Acid
Brain
Case-Control Studies
Cerebrovascular Circulation
Double-Blind Method
Fabry Disease
Humans
Image Processing, Computer-Assisted
Injections, Intravenous
Magnetic Resonance Imaging
Male
Reactive Oxygen Species
Spin Labels