Evidence map›Paper›PMID 26555554›Full record

ArticleNeurochemical research2016

Ethanol-Induced TLR4/NLRP3 Neuroinflammatory Response in Microglial Cells Promotes Leukocyte Infiltration Across the BBB.

Silvia Alfonso-Loeches, Juan Ureña-Peralta, M José Morillo-Bargues, Ulises Gómez-Pinedo, Consuelo Guerri

Abstract read
PubMed Publisher
In one paragraph

Article in Neurochemical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 123 citations in OpenAlex.

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  5. Headache associated with adverse cognitive trajectories in Chinese aging cohort: a group-based trajectory modeling study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  6. Article
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  8. Article
  9. Review
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  12. Article
  13. Thiamine Deficiency and Neuroinflammation Are Important Contributors to Alcohol Use Disorder.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Silvia Alfonso-LoechesMolecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, Eduardo Primo Yúfera 3, 46012, Valencia, Spain.
Juan Ureña-PeraltaMolecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, Eduardo Primo Yúfera 3, 46012, Valencia, Spain.
M José Morillo-BarguesMolecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, Eduardo Primo Yúfera 3, 46012, Valencia, Spain.
Ulises Gómez-PinedoDepartment of Regenerative Medicine/Neurology and Neurosurgery, Neuroscience Institute, Clinic San Carlos Hospital, IdISSC, Profesor Martín Lagos, S/N, 28040, Madrid, Spain.
Consuelo GuerriMolecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, Eduardo Primo Yúfera 3, 46012, Valencia, Spain. guerri@cipf.es.
Centro de Investigacion Principe Felipe · ESHospital Clínico San Carlos · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We reported that the ethanol-induced innate immune response by activating TLR4 signaling triggers gliosis and neuroinflammation. Ethanol also activates other immune receptors, such as NOD-like-receptors, and specifically NLRP3-inflammasome in astroglial cells, to stimulate caspase-1 cleavage and IL-1β and IL-18 cytokines production. Yet, whether microglia NLRs are also sensitive to the ethanol effects that contribute to neuroinflammation is uncertain. Using cerebral cortexes of the chronic alcohol-fed WT and TLR4(-/-) mice, we demonstrated that chronic ethanol treatment enhanced TLR4 mediated-NLRP3/Caspase-1 complex activation, and up-regulated pro-inflammatory cytokines and chemokines levels. Ethanol-induced NLRP3-inflammasome activation and mitochondria-ROS generation were also observed in cultured microglial cells. The up-regulation of CD45(high)/CD11b(+) cell populations and matrix metalloproteinase-9 levels was also noted in the cortexes of the ethanol-treated WT mice. Notably, elimination of the TLR4 function abolished most ethanol-induced neuroinflammatory effects. Thus, our results demonstrate that ethanol triggers TLR4-mediated NLRP3-inflammasome activation in glial cells, and suggest that microglia stimulation may compromise the permeability of blood-brain barrier events to contribute to ethanol-induced neuroinflammation and brain damage.

Indexed as

Blood-Brain BarrierAnimalsCarrier ProteinsCentral Nervous SystemEthanolFemaleLeukocytesMiceMice, Inbred C57BLMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinToll-Like Receptor 4Carrier ProteinsEthanolNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseTlr4 protein, mouseToll-Like Receptor 4AlcoholBBBLeukocyte infiltrationMatrix metalloproteinaseMicrogliaTLR4

Identifiers

PMID26555554
OpenAlexW2206384930

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.