ArticleThe Journal of clinical investigation2019
Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04776499 (Clinical Evaluation in Healthy Volunteers of Potential syneRgistic Vascular Effects of PrOpylthiouracil, Riociguat, and Perphenazine a Possible STROKE Medication), which is not on this map. Cited by 44 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical Evaluation in Healthy Volunteers of Potential syneRgistic Vascular Effects of PrOpylthiouracil, Riociguat, and Perphenazine a Possible STROKE Medication
Who cites it
44 citing papers in PubMed, 90 citations in OpenAlex.
- Synergistic Network Pharmacology: Preclinical Validation and Clinical Safety in Acute Ischemic Stroke.Journal of the American Heart Association · 2025Trial
- An Early Value Assessment of Biomarker-Guided Precision Medicine for Treatment-Resistant Hypertension: A Headroom and Threshold Analysis.Applied health economics and health policy · 2026Article
- Article
- From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.Journal of immunology research · 2026Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Combined Analysis of Human and Experimental Rat Samples Identified Biomarkers for Ischemic Stroke.Molecular neurobiology · 2025Article
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Innate Immunity Reimagined: Metabolic Reprogramming as a Gateway to Novel Therapeutics.International journal of biological sciences · 2025Review
- Delineating the NOX-Mediated Promising Therapeutic Strategies for the Management of Various Cardiovascular Disorders: A Comprehensive Review.Current vascular pharmacology · 2025Review
- Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer's Disease: Isoform-Specific Contributions.International journal of molecular sciences · 2024Review
- NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells.Antioxidants (Basel, Switzerland) · 2024Article
- The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials.Biochemical pharmacology · 2024Review
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Systems-level computational modeling in ischemic stroke: from cells to patients.Frontiers in physiology · 2024Review
- Endothelial NOX5 overexpression induces changes in the cardiac gene profile: potential impact in myocardial infarction?Journal of physiology and biochemistry · 2023Article
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- A high throughput blood-brain barrier model incorporating shear stress with improved predictive power for drug discovery.Biomicrofluidics · 2023Article
- Structure, regulation, and physiological functions of NADPH oxidase 5 (NOX5).Journal of physiology and biochemistry · 2023Review
- Immunomodulation: The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke.World journal of stem cells · 2023Review
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal of the occlusion being the only therapeutic option. Reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain barrier. Its mechanism, however, is unknown. Here, we identified type 5 NADPH oxidase (NOX5), a calcium-activated, ROS-forming enzyme, as the missing link. Using a humanized knockin (KI) mouse model and in vitro organotypic cultures, we found that reoxygenation or calcium overload increased brain ROS levels in a NOX5-dependent manner. In vivo, postischemic ROS formation, infarct volume, and functional outcomes were worsened in NOX5-KI mice. Of clinical and therapeutic relevance, in a human blood-barrier model, pharmacological NOX inhibition also prevented acute reoxygenation-induced leakage. Our data support further evaluation of poststroke recanalization in the presence of NOX inhibition for limiting stroke-induced damage.
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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.