ArticleNature medicine2010
Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 472 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
472 citing papers in PubMed, 2 syntheses or guidelines pooled it, 905 citations in OpenAlex.
- Meta-analysis of HMGB1 levels in the cerebrospinal fluid and serum of patients with epilepsy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Pooled it
- Progress in TLE treatment from 2003 to 2023: scientific measurement and visual analysis based on CiteSpace.Frontiers in neurology · 2023Pooled it
- Neurometabolite abnormalities and associations with epilepsy duration and cognition in patients with idiopathic generalized epilepsies.Epilepsia open · 2026Article
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- Sarcosine Remodels DNA Methylation-Linked Transcriptional Networks During Epileptogenesis in the Rat Rapid Hippocampal Kindling Model.International journal of molecular sciences · 2026Article
- cGAS-mediated type I IFN signaling contributes to disease progression in drug-refractory epilepsy.Nature neuroscience · 2026Article
- Selected Molecular Targets for Counteracting Epileptogenesis: What Do We Know About Its Effective Inhibition?Current issues in molecular biology · 2026Review
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Nonlinear Association Between the C-Reactive Protein-To-Albumin Ratio and Post-Stroke Epilepsy Risk.CNS neuroscience & therapeutics · 2026Article
- Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury.Journal of neuroinflammation · 2026Article
- Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy.Histology and histopathology · 2026Review
- Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.Nutrients · 2026Article
- TRPV4 is involved in NLRP3 and NLRP1 inflammasomes activation after pilocarpine-induced status epilepticus in mice : Concise title: TRPV4-mediated inflammasome activation in epilepsy.Cellular and molecular life sciences : CMLS · 2026Article
- WONOEP XVII appraisal: The immunopathogenesis of epilepsy.Epilepsia · 2026Review
- cGAS-mediated IFN-I signaling contributes to disease progression in drug-refractory epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Neuroimmune activation in temporal lobe epilepsy patients with worsening seizure following the COVID-19 pandemic: A [Science advances · 2026Article
- Neuronal Toll-like Receptor-4 regulation of Matrix Metalloproteinase-9 Activity Mediates Dentate Circuit Dysfunction after Traumatic Brain Injury.bioRxiv : the preprint server for biology · 2026Article
- Gastrodin alleviates neuronal damage in epileptic cell models by targeting P2RY12 to inhibit microglial hyperactivation.PloS one · 2026Article
- Clinical application of HMGB1-TLR4 signaling pathway-mediated neuroinflammatory markers in infantile epileptic spasms syndrome.Frontiers in immunology · 2026Article
- Association of atherogenic index of plasma and post-stroke epilepsy in patients with ischemic stroke: a multicenter retrospective study in China.Therapeutic advances in neurological disorders · 2026Article
412 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain inflammation is a major factor in epilepsy, but the impact of specific inflammatory mediators on neuronal excitability is incompletely understood. Using models of acute and chronic seizures in C57BL/6 mice, we discovered a proconvulsant pathway involving high-mobility group box-1 (HMGB1) release from neurons and glia and its interaction with Toll-like receptor 4 (TLR4), a key receptor of innate immunity. Antagonists of HMGB1 and TLR4 retard seizure precipitation and decrease acute and chronic seizure recurrence. TLR4-defective C3H/HeJ mice are resistant to kainate-induced seizures. The proconvulsant effects of HMGB1, like those of interleukin-1beta (IL-1beta), are partly mediated by ifenprodil-sensitive N-methyl-d-aspartate (NMDA) receptors. Increased expression of HMGB1 and TLR4 in human epileptogenic tissue, like that observed in the mouse model of chronic seizures, suggests a role for the HMGB1-TLR4 axis in human epilepsy. Thus, HMGB1-TLR4 signaling may contribute to generating and perpetuating seizures in humans and might be targeted to attain anticonvulsant effects in epilepsies that are currently resistant to drugs.
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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.