ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 333 papers, 1 of them a synthesis that pooled it.
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Who cites it
333 citing papers in PubMed, 1 synthesis or guideline pooled it, 574 citations in OpenAlex.
- Impact of Omega-3 Polyunsaturated Fatty Acids on Alcohol Use and Negative Consequences: A Systematic Review.Nutrition reviews · 2025Pooled it
- Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder.Alcohol, clinical & experimental research · 2025Trial
- Baseline C-reactive protein levels are predictive of treatment response to a neuroimmune modulator in individuals with an alcohol use disorder: a preliminary study.The American journal of drug and alcohol abuse · 2023Trial
- Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.Addiction biology · 2022Trial
- Ethanol drinking involves astrocytes in male Wistar rats.Behavioural brain research · 2026Article
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Heme Oxygenase-1 Contributes to Dampening Proinflammatory Activation in the Human Microglial Cell Line HMC3 and Controls the Transcription Factor IRF5.Biomolecules · 2026Article
- Adolescent intermittent ethanol exacerbates amyloid-β with age in the dorsal hippocampus of female TgF344-AD rats.Journal of Alzheimer's disease : JAD · 2026Article
- Global deletion ofbioRxiv : the preprint server for biology · 2026Article
- Plasma albumin and other indicators as risk factors for delayed neurocognitive recovery in elderly patients undergoing orthopedic surgery.BMC surgery · 2026Article
- Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder.Expert opinion on therapeutic targets · 2026Review
- Role of miRNAs from mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice.Neural regeneration research · 2026Article
- miR-146a-5p mitigates ethanol-induced neuroinflammation by targeting Btg2-dependent microglial activation.Malawi medical journal : the journal of Medical Association of Malawi · 2026Article
- Ethanol drinking involves astrocytes in male Wistar rats.bioRxiv : the preprint server for biology · 2026Article
- P2X7R Signaling and Differential Regulation of Neuroinflammatory and Behavior Responses in Male and Female Mice During Chronic Ethanol Exposure.International journal of molecular sciences · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Trigonelline protects against alcohol-induced brain damage by inhibition of oxidative stress, TLR4/NF-κB/proinflammatory cytokines pathway, and apoptosis.Iranian journal of basic medical sciences · 2026Article
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Astrocytes and Alcohol Throughout the Lifespan.Biological psychiatry · 2026Review
- The Role of Toll-like Receptor 3 Signaling in Cognitive Impairment Induced by Propofol Addiction.Molecular neurobiology · 2025Article
273 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation. This study aims to establish the potential role of TLR4 in both ethanol-induced glial activation and brain damage. Here we report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells since the knockdown of TLR4, by using both small interfering RNA or cells from TLR4-deficient mice, abolished the activation of microtubule-associated protein kinase and nuclear factor-kappaB pathways and the production of inflammatory mediators by astrocytes. Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates the immunoreactive levels of CD11b (microglial marker) and glial fibrillary acidic protein (astrocyte marker), and also increases caspase-3 activity and inducible nitric oxide synthase, COX-2, and cytokine levels [interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6] in the cerebral cortex of female wild-type mice, TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.
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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.