Related Experiment Video
Updated: Apr 5, 2026
Paired Cisterna Magna Nanoinjection and Laser Speckle Contrast Imaging Assay to Study Cerebral Blood Flow Regulation In Vivo
Published on: July 8, 2025
Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role for Hypoxia-Inducible Transcription
Farzaneh A Sorond1, Can Ozan Tan2, Sarah LaRose2
1From the Stroke Division, Department of Neurology (F.A.S., S.L.R., A.D.M.) and Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology (R.F., S.R.), Brigham and Women's Hospital, Boston, MA; Cardiovascular Research Laboratory, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA (C.O.T.); Department of Medicine, Hebrew SeniorLife Institute for Aging Research, Boston, MA (L.A.L.); Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA (L.A.L.); and Department of Neurology, Physical Medicine and Rehabilitation, Obstetrics and Gynecology, and Medicine, Harvard Medical School, Boston, MA (F.A.S., C.O.T., R.F., L.A.L.). fsorond@partners.org.
Background And Purpose:
Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether hypoxia-inducible transcription factor-1 activation may be temporally correlated with vascular changes.
Methods:
We assessed cerebrovascular function (autoregulation, vasoreactivity, and neurovascular coupling) and serum concentrations of vascular endothelial growth factor and erythropoietin, as representative measures of hypoxia-inducible transcription factor-1 activation, during 6 hours of deferoxamine infusion in 24 young and 24 older healthy volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. Vascular endothelial growth factor and erythropoietin serum protein assays were conducted using the Meso Scale Discovery platform.
Results:
Deferoxamine elicited a strong age- and time-dependent increase in the plasma concentrations of erythropoietin and vascular endothelial growth factor, which persisted ≤3 hours post infusion (age effect P=0.04; treatment×time P<0.01). Deferoxamine infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment×time P<0.01; age P<0.01) and cerebral autoregulation (gain: age×time×treatment P=0.04).
Conclusions:
Deferoxamine infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum vascular endothelial growth factor and erythropoietin concentrations is supportive of shared hypoxia-inducible transcription factor-1-regulated pathways. Therefore, pharmacological activation of hypoxia-inducible transcription factor-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT013655104.
More Related Videos
09:48Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
08:15Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:27Regulation of Stroke Volume
Preload refers to the degree of stretch on the heart before it contracts. It's analogous to the stretching of a rubber band; the more it's stretched, the more forcefully it snaps back. This concept is encapsulated in the Frank-Starling law of the...