ArticleProceedings of the National Academy of Sciences of the United States of America2022
Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The Dual Role of Connexins in Stroke, Neurotrauma, Neurodegenerative and Psychiatric Disorders: A Global Systematic Review.Molecules (Basel, Switzerland) · 2026Pooled it
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- Neuroinflammation in Epilepsy: Biochemical and Molecular Mechanisms and Implications for Natural Product-Driven Drug Discovery.International journal of molecular sciences · 2026Review
- Uncovering the Key Circuit FOSL2/FOS/EGR3/EGR1, Contributing to the Hyperexcitability of Excitatory Neurons in the Epileptic Temporal Cortex and Hippocampus.International journal of molecular sciences · 2026Article
- Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Structure-based virtual screening for selective connexin hemichannel blockers: a historical perspective on the discovery of a small organic inhibitor.Frontiers in pharmacology · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Boldo leaves reduce seizures, neuroinflammation, and hemichannel activity in a murine model of chronic epilepsy.Biological research · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates cognitive deficits in a mouse model of amyloidosis.Nature communications · 2025Article
- Coordination acid-engineered Prussian Blue affects glycometabolic reprogramming in microglia for epileptic treatment.Journal of nanobiotechnology · 2025Article
- Repression of Connexin26 hemichannel activity protects the barrier function of respiratory airway epithelial cells against LPS-induced alteration.Cell communication and signaling : CCS · 2025Article
- The Role of Neuroinflammation and Network Anomalies in Drug-Resistant Epilepsy.Neuroscience bulletin · 2025Review
- Research progress of connexins in epileptogensis.Acta epileptologica · 2025Review
- Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Review
- Advances in understanding the role of inflammatory factors and immune cells in the pathology of epilepsy, mediated by neuroimmune interactions within the gut-brain axis.Frontiers in cell and developmental biology · 2025Review
- Maresin 1 Alleviates Seizure Symptoms by Modulating the Crosstalk Between Inflammation and Ferroptosis.Journal of inflammation research · 2025Article
- Boldine as a neuroprotective agent against motor neuron degeneration in models of amyotrophic lateral sclerosis.Frontiers in cellular neuroscience · 2025Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy, yet approximately one-third of patients are refractory to current anticonvulsive drugs, which target neurons and synapses. Astrocytic and microglial dysfunction is commonly found in epileptic foci and has been shown to contribute to neuroinflammation and hyperexcitability in chronic epilepsy. Accumulating evidence points to a key role for glial hemichannels in epilepsy, but inhibiting both connexin (Cx) gap junctions and hemichannels can lead to undesirable side effects because the former coordinate physiological functions of cell assemblies. It would be a great benefit to use an orally available small molecule to block hemichannels to alleviate epileptic symptoms. Here, we explored the effect of D4, a newly developed compound that inhibits the Cx hemichannels but not Cx gap junctions using the pilocarpine mouse model of TLE. In vitro application of D4 caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity. Moreover, preadministration of D4 in vivo effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate. Posttreatment with a single dose of D4 in vivo has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine. Collectively, these results indicate that targeting Cx hemichannels by D4 is an effective and promising strategy for treating epilepsy in which neuroinflammation plays a critical role.
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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.