Iron neurotoxicity in ischemic and hemorrhagic stroke

Abstract

Disturbance of iron homeostasis in the brain plays an important pathogenic role in aggravating secondary neuronal injury and influencing recovery and functional outcome following cerebral ischemia or hemorrhage via several mechanisms including the release of redox-active iron, depletion of cellular energy stores, production of superoxide and hydroxyl radicals, and lipid peroxidation. We systematically review the currently available preclinical and clinical evidence supporting the role of iron-mediated toxicity in ischemic and hemorrhagic strokes, and its potential mechanisms. We also highlight the strategies being developed for the reduction of iron toxicity in stroke patients, and novel clinical therapeutic trials of iron-modifying agents in patients with ischemic and hemorrhagic strokes. Targeting iron toxicity as a treatment for stroke is an appealing and promising option. Future clinical studies are needed to translate a plethora of preclinical data into the clinical setting.