Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible transcription factor 1
author: Farzaneh A Sorond; Michele L Shaffer; Andrew L Kung; Lewis A Lipsitz
source date: 2008-11-18
language: en

Abstract

Finding an effective means to improve cerebral perfusion during hypoxic-ischemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that Desferroxamine activates hypoxia inducible transcription factor-1, reduces brain damage and promotes functional recovery. Our study was designed to investigate the effects of Desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blinded 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 hypoxia inducible transcription factor-1 protein and serum lactate dehydrogenase concentrations in response to 8 hours of Desferroxamine versus 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 increased hypoxia inducible transcription factor-1 protein concentration as well as hypoxia inducible transcription factor-1 transcriptional activation as measured by serum lactate dehydrogenase concentration. Our findings provide preliminary data suggesting that activators of hypoxia inducible transcription factor-1, such as Desferroxamine, may protect neurons against ischemic injury by dilating cerebral vessels and enhancing cerebral perfusion.