ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2011
Prophylactic neuroprotection against stroke: low-dose, prolonged treatment with deferoxamine or deferasirox establishes prolonged neuroprotection independent of HIF-1 function.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Iron chelators for acute stroke.The Cochrane database of systematic reviews · 2020Pooled it
- Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.Scientific reports · 2016Pooled it
- Ferroptosis and Its Crosstalk with Other Cell Death Modes in Ischemic Stroke.Current medicinal chemistry · 2026Review
- Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke.Journal of translational medicine · 2024Article
- Activation of the hypoxia-inducible factor pathway protects against acute ischemic stroke by reprogramming central carbon metabolism.Theranostics · 2024Article
- Out of the core: the impact of focal ischemia in regions beyond the penumbra.Frontiers in cellular neuroscience · 2024Review
- Regulated necrosis pathways: a potential target for ischemic stroke.Burns & trauma · 2023Review
- Therapeutic potential of iron chelators in retinal vascular diseases.International journal of ophthalmology · 2023Review
- Ferroptosis-A Novel Mechanism With Multifaceted Actions on Stroke.Frontiers in neurology · 2022Review
- Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial.Antioxidants (Basel, Switzerland) · 2021Article
- Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia.Biomolecules · 2021Review
- Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Deferasirox, a trivalent iron chelator, ameliorates neuronal damage in hemorrhagic stroke models.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Targeting metabolic activity in high-risk neuroblastoma through Monocarboxylate Transporter 1 (MCT1) inhibition.Oncogene · 2020Article
- Intranasal deferoxamine can improve memory in healthy C57 mice, suggesting a partially non-disease-specific pathway of functional neurologic improvement.Brain and behavior · 2020Article
- The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis.Frontiers in cellular neuroscience · 2020Article
- Collagen Nanoparticle-Mediated Brain Silymarin Delivery: An Approach for Treating Cerebral Ischemia and Reperfusion-Induced Brain Injury.Frontiers in neuroscience · 2020Article
- Poster Viewing Sessions PB01-B01 to PB03-V09.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Reactive Oxygen Species Formation in the Brain at Different Oxygen Levels: The Role of Hypoxia Inducible Factors.Frontiers in cell and developmental biology · 2018Review
- Hypoxia Mimetic Agents for Ischemic Stroke.Frontiers in cell and developmental biology · 2018Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Prophylactic neuroprotection against stroke could reduce stroke burden in thousands of patients at high risk of stroke, including those with recent transient ischemic attacks (TIAs). Prolyl hydroxylase inhibitors (PHIs), such as deferoxamine (DFO), reduce stroke volume when administered at high doses in the peristroke period, which is largely mediated by the hypoxia-inducible transcription factor (HIF-1). Yet, in vitro experiments suggest that PHIs may also induce neuroprotection independent of HIF-1. In this study, we examine chronic, prophylactic, low-dose treatment with DFO, or another iron chelator deferasirox (DFR), to determine whether they are neuroprotective with this paradigm and mediate their effects through a HIF-1-dependent mechanism. In fact, prophylactic administration of low-dose DFO or DFR significantly reduces stroke volume. Surprisingly, DFO remained neuroprotective in mice haploinsufficient for HIF-1 (HIF-1+/-) and transgenic mice with conditional loss of HIF-1 function in neurons and astrocytes. Similarly, DFR was neuroprotective in HIF-1+/- mice. Neither DFO nor DFR induced expression of HIF-1 targets. Thus, low-dose chronic administration of DFO or DFR induced a prolonged neuroprotective state independent of HIF-1 function. As DFR is an orally administered and well-tolerated medication in clinical use, it has promise for prophylaxis against stroke in patients at high risk of stroke.
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