ArticleJCI insight2022
Targeting gliovascular connexins prevents inflammatory blood-brain barrier leakage and astrogliosis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Bridging Hypoxia and Vision Loss: The Emerging Role of Connexins in Local and Systemic Eye Diseases.International journal of molecular sciences · 2026Review
- Integrated bioinformatics and experimental validation identifies SOX2 as a key therapeutic target for chronic atrophic gastritis/gastric cancer-depression comorbidity.Frontiers in oncology · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus.Frontiers in neuroanatomy · 2026Article
- Brain endothelial homeostasis in psychiatric disorders: mechanisms, evidence, and translational opportunities.Frontiers in cellular neuroscience · 2026Review
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- α, δ‑ACS pharmacology & translational science · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Across Barriers: Blood-Brain and Gut Barrier Signaling in Psychiatric Disorders.Journal of neurochemistry · 2025Review
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Viruses and the Brain-A Relationship Prone to Trouble.Viruses · 2025Review
- Connexin-43 in Cancer: Above and Beyond Gap Junctions!Cancers · 2024Review
- Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS.NeuroImmune pharmacology and therapeutics · 2024Article
- Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.Magnetic resonance in medicine · 2024Article
- Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model.Scientific reports · 2024Article
- Spatiotemporal Insights into Glioma Oncostream Dynamics: Unraveling Formation, Stability, and Disassembly Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcriptomic profiling of "brain-eating amoeba"Frontiers in cellular and infection microbiology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-brain barrier is formed by capillary endothelial cells expressing connexin 37 (Cx37), Cx40, and Cx43 and is joined by closely apposed astrocytes expressing Cx43 and Cx30. We investigated whether connexin-targeting peptides could limit barrier leakage triggered by LPS-induced systemic inflammation in mice. Intraperitoneal LPS administration increased endothelial and astrocytic Cx43 expression; elevated TNF-α, IL-1β, IFN-γ, and IL-6 in plasma and IL-6 in the brain; and induced barrier leakage recorded over 24 hours. Barrier leakage was largely prevented by global Cx43 knockdown and Cx43/Cx30 double knockout in astrocytes, slightly diminished by endothelial Cx43 knockout, and not protected by global Cx30 knockout. Intravenous administration of Gap27 or Tat-Gap19 peptides just before LPS also prevented barrier leakage, and intravenously administered BAPTA-AM to chelate intracellular calcium was equally effective. Patch-clamp experiments demonstrated LPS-induced Cx43 hemichannel opening in endothelial cells, which was suppressed by Gap27, Gap19, and BAPTA. LPS additionally triggered astrogliosis that was prevented by intravenous Tat-Gap19 or BAPTA-AM. Cortically applied Tat-Gap19 or BAPTA-AM to primarily target astrocytes also strongly diminished barrier leakage. In vivo dye uptake and in vitro patch-clamp showed Cx43 hemichannel opening in astrocytes that was induced by IL-6 in a calcium-dependent manner. We conclude that targeting endothelial and astrocytic connexins is a powerful approach to limit barrier failure and astrogliosis.
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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.