ArticleThe Journal of experimental medicine2020
Endothelial Cdk5 deficit leads to the development of spontaneous epilepsy through CXCL1/CXCR2-mediated reactive astrogliosis.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Myeloid PD-1 Regulates Astrocyte Development and Leads to Active Behaviours.Cell proliferation · 2026Article
- Silencing C-X-C motif chemokine receptor inhibited autophagy of hippocampal neurons in epileptic mice by upregulating TWIK-related KCytoJournal · 2026Article
- Apigenin Regulating PI3K/AKT Pathway to Improve Depressive Behavior in Epileptic Rats.Combinatorial chemistry & high throughput screening · 2026Article
- Article
- Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review).International journal of molecular medicine · 2025Review
- The Role of Neuroinflammation and Network Anomalies in Drug-Resistant Epilepsy.Neuroscience bulletin · 2025Review
- Reparixin as a Potential Antiepileptogenic Agent: Modulation of the CXCL1-CXCR1/2 Axis and Seizure Activity in a Kindling Rat Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2025Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Endothelial Myosin IIA Is Required for the Maintenance of Blood-Brain Barrier Integrity.Cells · 2024Article
- Molecular Genetics of Acquired Temporal Lobe Epilepsy.Biomolecules · 2024Review
- Review
- The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy.Neuroscience bulletin · 2024Review
- Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism.International journal of molecular sciences · 2024Review
- A novel animal model of spontaneous epilepsy: Cdk5 knockout in pericyte-specific mice.Frontiers in cellular neuroscience · 2024Article
- The m6A reader YTHDC2 promotes the pathophysiology of temporal lobe epilepsy by modulating SLC7A11-dependent glutamate dysregulation in astrocytes.Theranostics · 2024Article
- Evaluation of BR1 and BI30 AAVs for Brain Endothelial Tropism.ASN neuro · 2024Article
- AAV-BR1 does not target endothelial cells in Sprague Dawley rats unlike in mice.microPublication biology · 2024Article
- Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.Journal of neuroinflammation · 2023Article
- VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration.Molecular psychiatry · 2023Article
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy.
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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.