Finding an effective means to improve cerebral perfusion during hypoxic/ischaemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that desferroxamine activates HIF-1 (hypoxia-inducible factor-1), reduces brain damage and promotes functional recovery. The present study was designed to investigate the effects of desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blind placebo-controlled crossover study. We measured cerebral blood flow velocity by transcranial Doppler ultrasonography in the middle cerebral artery, arterial blood pressure, end-tidal CO2, as well as HIF-1 protein and serum lactate dehydrogenase concentrations in response to 8 h of desferroxamine compared with placebo infusion. Cerebrovascular resistance was calculated from the ratio of steady-state beat-to-beat values for blood pressure to blood flow velocity. We found that desferroxamine infusion was associated with a significant cerebral vasodilation. Moreover, decreased cerebrovascular resistance was temporally correlated with an increased HIF-1 protein concentration as well as HIF-1 transcriptional activation, as measured by serum lactate dehydrogenase concentration. The findings of the present study provide preliminary data suggesting that activators of HIF-1, such as desferroxamine, may protect neurons against ischaemic injury by dilating cerebral vessels and enhancing cerebral perfusion.
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May 2009
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Research Article|
April 15 2009
Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1
Farzaneh A. Sorond;
*Department of Neurology, Stroke Division, Brigham and Women's Hospital, Boston, MA 02115, U.S.A.
†Institute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, U.S.A.
Correspondence: Dr Farzaneh A. Sorond (email fsorond@partners.org).
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Michele L. Shaffer;
Michele L. Shaffer
‡Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033-0855, U.S.A.
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Andrew L. Kung;
Andrew L. Kung
§Dana Farber Cancer Institute, Boston, MA 02115, U.S.A.
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Lewis A. Lipsitz
Lewis A. Lipsitz
†Institute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, U.S.A.
∥Department of Medicine, Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02215, U.S.A.
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Clin Sci (Lond) (2009) 116 (10): 771–779.
Article history
Received:
July 17 2008
Revision Received:
October 09 2008
Accepted:
November 18 2008
Accepted Manuscript online:
November 18 2008
Citation
Farzaneh A. Sorond, Michele L. Shaffer, Andrew L. Kung, Lewis A. Lipsitz; Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1. Clin Sci (Lond) 1 May 2009; 116 (10): 771–779. doi: https://doi.org/10.1042/CS20080320
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