ArticleProceedings of the National Academy of Sciences of the United States of America2024
Endothelial peroxiredoxin-4 is indispensable for blood-brain barrier integrity and long-term functional recovery after ischemic stroke.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 16 citations in OpenAlex.
- Total flavones of Rhododendron protect against BBB injury following cerebral ischemia/reperfusion via promoting astrocytic polarization towards A2 subtype.Apoptosis : an international journal on programmed cell death · 2026Article
- Intra-Arterial Selective Hypothermic Human Serum Albumin Perfusion Attenuates Cerebral Ischemia-Reperfusion Injury.Translational stroke research · 2026Article
- The Role of Peroxiredoxins in the Mechanisms of Oxidative Stress in Patients After Aneurysmal Subarachnoid Hemorrhage.International journal of molecular sciences · 2026Review
- Peroxiredoxins in Stroke: Friends and Foes.Cells · 2026Review
- The Potential of Neural Stem Cell-derived Exosomes for the Treatment of Ischemic Stroke.Stem cell reviews and reports · 2026Review
- The endothelial activation and stress index as a key prognostic marker in severe ischemic stroke.European journal of medical research · 2026Article
- Stimuli-responsive nanozyme-hydrogel systems for ischemic stroke: toward spatiotemporal catalytic control of the neurovascular unit.Frontiers in neurology · 2026Review
- Nitro-oleic acid activation of endothelial PPARγ signaling pathway alleviates neurovascular injury and improves functional outcomes in ischemic stroke.Brain pathology (Zurich, Switzerland) · 2026Article
- Iron enhances reactive oxygen species generation and initiates neutrophil extracellular traps formation on the endothelium to exacerbate stroke.Journal of cell communication and signaling · 2025Article
- Immunological Mechanisms and Therapeutic Strategies in Cerebral Ischemia-Reperfusion Injury: From Inflammatory Response to Neurorepair.International journal of molecular sciences · 2025Review
- Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS.Antioxidants (Basel, Switzerland) · 2025Article
- Aging, vascular dysfunction, and the blood-brain barrier: unveiling the pathophysiology of stroke in older adults.Biogerontology · 2025Review
- Caloric Restriction Preserves BBB Integrity After Transient Focal Cerebral Ischemia Through Reducing Neutrophil Infiltration.CNS neuroscience & therapeutics · 2025Article
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- Article
- Early and enduring: Targeting the endothelium for blood-brain barrier protection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy - A Comprehensive Literature Review.International journal of nanomedicine · 2024Review
- Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.