Oxidative Stress Mechanisms in Ischemic Stroke

Ischaemic stroke arises from an abrupt interruption of cerebral blood supply, depriving neurons of oxygen and glucose. The ensuing energy deficit impairs ionic homeostasis, mitochondrial respiration and adenosine triphosphate synthesis. Restoration of blood flow triggers a surge in reactive oxygen and nitrogen species that oxidise lipids, proteins and nucleic acids, damage endothelial cells and disrupt the blood–brain barrier. Key enzymatic sources of oxidative stress include mitochondrial complex I, NADPH oxidases and myeloperoxidase in infiltrating neutrophils and activated microglia. Oxidative modifications of signalling proteins such as high-mobility group box 1 amplify neuroinflammation and apoptosis, while depletion of endogenous antioxidants—including glutathione, superoxide dismutase and catalase—exacerbates cellular injury. This multifaceted oxidative cascade contributes to infarct expansion, neurological deficits and long-term disability. A growing understanding of these mechanisms underpins the development of biomarkers for injury severity and targeted therapies that restore redox balance, protect mitochondrial function and modulate immune responses in diverse patient populations.

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Oxidative Stress Mechanisms in Ischemic Stroke publication trend

The graph below shows the total number of articles in oxidative stress mechanisms in ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can oxidise cellular components.

Myeloperoxidase (MPO): An enzyme released by neutrophils and microglia that produces potent oxidants including hypochlorous acid.

Hypochlorous acid (HOCl): A strong oxidant generated by MPO that can modify proteins and lipids.

Glutathione (GSH): A tripeptide antioxidant that neutralises ROS and maintains redox balance.

Mitochondrial complex I: The first enzyme of the electron transport chain, whose dysfunction contributes to oxidative stress on reperfusion.

Ischaemia–reperfusion: The sequence of oxygen and nutrient deprivation followed by restoration of blood flow, often leading to oxidative injury.

References

1. Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia–reperfusion injury. Journal of Neuroinflammation (2024).
2. Aging Intensifies Myeloperoxidase Activity after Ischemic Stroke. Aging and Disease (2024).
3. Critical Role of Flavin and Glutathione in Complex I–Mediated Bioenergetic Failure in Brain Ischemia/Reperfusion Injury. Stroke (2018).
4. Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke. Antioxidants (2021).