ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2021
Tight junctions in the blood-brain barrier promote edema formation and infarct size in stroke - Ambivalent effects of sealing proteins.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Nanoscopic analysis of tight junction organization in in vitro blood-brain barrier models.Fluids and barriers of the CNS · 2026Article
- CRISPR-Based Therapy for Ischemic Stroke: A Narrative Review.Cellular and molecular neurobiology · 2026Review
- Blood-Brain Barrier Permeability Dynamics and Mediation of Triglyceride-Glucose Index on Acute Ischemic Stroke Outcomes.Journal of the American Heart Association · 2026Article
- Intranasal delivery route for neurodegenerative diseases: recent insights and future directions.Drug delivery and translational research · 2026Review
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- Effect of Methylprednisolone on Ischemic Brain Edema After Temporary Occlusion of the Middle Cerebral Artery in Rats.Physiological research · 2025Article
- The Relationship Between Clinical Features of Ischemic Stroke and miRNA Expression in Stroke Patients: A Systematic Review.Neurology international · 2025Review
- Generation of Advanced Blood-Brain Barrier Spheroids Using Human-Induced Pluripotent Stem Cell-Derived Brain Capillary Endothelial-Like Cells.Advanced biology · 2025Article
- Molecular Motors in Blood-Brain Barrier Maintenance by Astrocytes.Brain sciences · 2025Review
- Endothelial Cells and the Blood-Brain Barrier: Critical Determinants of Ineffective Reperfusion in Stroke.The European journal of neuroscience · 2025Review
- Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.Cancers · 2025Review
- BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.Autophagy reports · 2025Review
- The Role of Gut Microbiota in Blood-Brain Barrier Disruption after Stroke.Molecular neurobiology · 2024Review
- Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier.Fluids and barriers of the CNS · 2024Review
- Brain repair mechanisms after cell therapy for stroke.Brain : a journal of neurology · 2024Review
- The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials.Biochemical pharmacology · 2024Review
- Indole-3-Acetic Acid Protects Against Lipopolysaccharide-induced Endothelial Cell Dysfunction and Lung Injury through the Activation of USP40.American journal of respiratory cell and molecular biology · 2024Article
- Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury.Neuroscience bulletin · 2024Article
- Claudin and transmembrane receptor protein gene expressions are reversely correlated in peritumoral brain edema.Cancer medicine · 2024Article
- Propofol Suppresses LPS-induced BBB Damage by Regulating miR-130a-5p/ZO-1 Axis.Molecular biotechnology · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors.
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Abstract
The outcome of stroke is greatly influenced by the state of the blood-brain barrier (BBB). The BBB endothelium is sealed paracellularly by tight junction (TJ) proteins, i.e., claudins (Cldns) and the redox regulator occludin. Functions of Cldn3 and occludin at the BBB are largely unknown, particularly after stroke. We address the effects of Cldn3 deficiency and stress factors on the BBB and its TJs. Cldn3 tightened the BBB for small molecules and ions, limited endothelial endocytosis, strengthened the TJ structure and controlled Cldn1 expression. After middle cerebral artery occlusion (MCAO) and 3-h reperfusion or hypoxia of isolated brain capillaries, Cldn1, Cldn3 and occludin were downregulated. In Cldn3 knockout mice (C3KO), the reduction in Cldn1 was even greater and TJ ultrastructure was impaired; 48 h after MCAO of wt mice, infarct volumes were enlarged and edema developed, but endothelial TJs were preserved. In contrast, junctional localization of Cldn5 and occludin, TJ density, swelling and infarction size were reduced in affected brain areas of C3KO. Taken together, Cldn3 and occludin protect TJs in stroke, and this keeps the BBB intact. However, functional Cldn3, Cldn3-regulated TJ proteins and occludin promote edema and infarction, which suggests that TJ modulation could improve the outcome of stroke.
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