ArticleNature communications2022
Microvascular stabilization via blood-brain barrier regulation prevents seizure activity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Pooled it
- A dual-modality workflow for quantifying microvascular structure in human temporal lobe epilepsy.IBRO neuroscience reports · 2026Article
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Liver-derived complement component 3 promotes the susceptibility to stress-induced depression by impairing blood-brain barrier integrity.Molecular psychiatry · 2026Article
- Brain endothelial GαEBioMedicine · 2026Article
- 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
- In Vitro Models of Sturge-Weber Syndrome: Strengths, Limitations, and Future Goals.International journal of molecular sciences · 2026Review
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- EHD4 and ASAP2 are critical negative regulators of the claudin-5-based endothelial barrier.The FEBS journal · 2026Article
- Nanoscopic analysis of tight junction organization in in vitro blood-brain barrier models.Fluids and barriers of the CNS · 2026Article
- Chemokine Networks in Blood-Brain Barrier Regulation: Bidirectional Mechanisms, Clinical Translation, and Precision Therapeutic Prospects.Biomolecules · 2026Review
- Postoperative neurocognitive disorder: migration and crosstalk of inflammation in the peripheral and central nervous system.Perioperative medicine (London, England) · 2026Review
- Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Occludin deficiency is associated with developmental impairment, locomotor dysfunction, and social deficiencies.Tissue barriers · 2026Article
- DPP-4 inhibitors in drug-resistant epilepsy: a hypothesized mechanism via the gut microbiota-short-chain fatty acids-glucagon-like peptide-1 axis.Frontiers in immunology · 2026Review
- Glymphatic system dysfunction in temporal lobe epilepsy with hippocampal sclerosis: MRI-based evaluation of circulatory markers and disease progression.Frontiers in neuroscience · 2026Article
- Hydroxychloroquine Prevents High-altitude Cerebral Edema by Inhibiting Endothelial Claudin-5 Autophagic Degradation.Current neuropharmacology · 2026Article
- Polysaccharide-rich birch sap attenuates kainic acid-induced acute seizures by suppressing TLR4/NF-κB-mediated inflammation and preserving blood-brain barrier and glutamate homeostasis.Frontiers in pharmacology · 2026Article
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients.
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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.