Rationale and Current Evidence for Testing Iron Chelators for Treating Stroke
Purpose of Review
To discuss the mechanisms of iron regulation in the brain and the pathophysiological role of deregulation of iron homeostasis following a stroke, and to review existing evidence supporting the potential role of iron chelators in the treatment of ischemic and hemorrhagic stroke.
In recent years, accumulating evidence has highlighted the role of neuroinflammation in neurological injury after ischemic and hemorrhagic stroke, and that free iron is central to this process. Via the Fenton reaction, free iron catalyzes the conversion of superoxide ion and hydrogen peroxide into hydroxyl radicals, which promote oxidative stress.
Advances in our understanding of changes in brain iron metabolism and its relationship to neuronal injury in stroke could provide new therapeutic strategies to improve the outcome of stroke patients. Pharmacological agents targeting brain iron regulation hold promise as potentially effective treatments in both ischemic and hemorrhagic stroke.
KeywordsIron Chelators Ischemic stroke Cerebral hemorrhage Inflammation Neuroprotection
Dr. Hanafy receives support from the National Institute of Neurological Disorders and Stroke (R21NS099606) and the American Heart Association Grant in Aid (17GRNT33670058). Dr. Selim is partly supported by the National Institute of Neurological Disorders and Stroke (U01NS 074425).
Compliance with Ethical Standards
Conflict of Interest
Khalid A. Hanafy, Joao A. Gomes, and Magdy Selim declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This is a review article so we have referenced studies done in humans and animals, but these studies were not done as part of this article, and they are just referenced here. For those studies performed by the authors, all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. And all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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