ArticleJournal of neuroinflammation2020
Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 121 citations in OpenAlex.
- Astrocyte reactivity by alcohol dependence in the central amygdala.Brain, behavior, and immunity · 2026Article
- CD44 as a Conserved Biomarker and Functional Modulator of Neuroinflammation in Multiple Sclerosis and Beyond.Molecular neurobiology · 2026Article
- Ethanol exacerbates post-burn neuroinflammation and gut-brain barrier dysfunction which are associated with microbiome changes.Alcohol (Fayetteville, N.Y.) · 2026Review
- Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026Article
- Naltrexone treatment improves anxiety- and depression-like behavior in alcohol-exposed mice.Behavioural pharmacology · 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
- Timeless and Stainless Alcohol: Concentric Waves from Its Oxidative Metabolism and Related Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- The effects of alcohol dependence on the CSF proteome in mice: Evidence for blood-brain barrier dysfunction and neuroinflammation.Neurobiology of disease · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Article
- Neurotoxicity of Chronic Alcohol Exposure: Mechanistic Insights, Cellular Disruption, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Impact of adolescent ethanol binge on serotonin signaling and pain sensitivity post-withdrawal.Alcohol (Fayetteville, N.Y.) · 2025Article
- The effects of Alcohol Dependence on the CSF Proteome in Mice: Evidence for Blood-Brain Barrier Dysfunction and Neuroinflammation.bioRxiv : the preprint server for biology · 2025Article
- Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease.Alcohol (Fayetteville, N.Y.) · 2025Review
- Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.Brain, behavior, and immunity · 2025Review
- Proinflammatory Risk Factors in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis.Antioxidants (Basel, Switzerland) · 2025Review
- Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder.Nature communications · 2025Article
- Alcohol-Induced Oxidative Stress and Gut-Liver-Brain Crosstalk: Expanding the Paradigm from ALD to MetALD.Antioxidants (Basel, Switzerland) · 2025Review
- Chronic alcohol consumption induces phenotypic and functional alterations consistent with a hyper-inflammatory state in peripheral blood mononuclear cell-derived microglia in a rhesus macaque model.Brain, behavior, and immunity · 2025Article
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChronic alcohol consumption is associated with neuroinflammation, neuronal damage, and behavioral alterations including addiction. Alcohol-induced neuroinflammation is characterized by increased expression of proinflammatory cytokines (including TNFα, IL-1β, and CCL2) and microglial activation. We hypothesized chronic alcohol consumption results in peripheral immune cell infiltration to the CNS. Since chemotaxis through the CCL2-CCR2 signaling axis is critical for macrophage recruitment peripherally and centrally, we further hypothesized that blockade of CCL2 signaling using the dual CCR2/5 inhibitor cenicriviroc (CVC) would prevent alcohol-induced CNS infiltration of peripheral macrophages and alter the neuroinflammatory state in the brain after chronic alcohol consumption.
methodsC57BL/6J female mice were fed an isocaloric or 5% (v/v) ethanol Lieber DeCarli diet for 6 weeks. Some mice received daily injections of CVC. Microglia and infiltrating macrophages were characterized and quantified by flow cytometry and visualized using CX3CR1
resultsChronic alcohol consumption induced microglia activation and peripheral macrophage infiltration in the CNS, particularly in the hippocampus. Treatment with CVC abrogated ethanol-induced recruitment of peripheral macrophages and partially reversed microglia activation. Furthermore, the expression of proinflammatory markers was upregulated by chronic alcohol consumption in various regions of the brain, including the cortex, hippocampus, and cerebellum. Inhibition of CCR2/5 decreased alcohol-mediated expression of inflammatory markers. Finally, microglia function was impaired by chronic alcohol consumption and restored by CVC treatment. CVC treatment did not change the ethanol consumption or preference of mice in the two-bottle choice test.
conclusionsTogether, our data establish that chronic alcohol consumption promotes the recruitment of peripheral macrophages into the CNS and microglia alterations through the CCR2/5 axis. Therefore, further exploration of the CCR2/5 axis as a modulator of neuroinflammation may offer a potential therapeutic approach for the treatment of alcohol-associated neuroinflammation.
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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.