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Clin Sci (Lond). 2009 May;116(10):771-9. doi: 10.1042/CS20080320.

Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1.

Author information

1
Department of Neurology, Stroke Division, Brigham and Women's Hospital, Boston, MA 02115, USA. fsorond@partners.org

Abstract

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 CO(2), 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.

PMID:
19014354
PMCID:
PMC2854553
DOI:
10.1042/CS20080320
[Indexed for MEDLINE]
Free PMC Article

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