Evidence map›Paper›PMID 31074003›Full record

ArticleBritish journal of pharmacology2019

Early toll-like receptor 4 blockade reduces ROS and inflammation triggered by microglial pro-inflammatory phenotype in rodent and human brain ischaemia models.

Esther Parada, Ana I Casas, Alejandra Palomino-Antolin, Vanessa Gómez-Rangel, Alfonso Rubio-Navarro, Victor Farré-Alins, Paloma Narros-Fernandez, Melania Guerrero-Hue, Juan Antonio Moreno, Juliana M Rosa and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 57 citations in OpenAlex.

  1. Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026
    Article
  2. The Role of TNF-α in Ischemic Stroke.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Review
  5. The Extract ofCurrent neuropharmacology · 2025
    Article
  6. Ischemic stroke and diabetes: a TLR4-mediated neuroinflammatory perspective.Journal of molecular medicine (Berlin, Germany) · 2024
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Pharmaceutical biology · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Regulation of blood-brain barrier integrity by microglia in health and disease: A therapeutic opportunity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Review
  20. Review
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

13 authors at 4 institutions in 2 countries.

Esther ParadaMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
Ana I CasasDepartment of Pharmacology and Personalised Medicine, CARIM, Maastricht University, Maastricht, The Netherlands.
Alejandra Palomino-AntolinMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
Vanessa Gómez-RangelMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
Alfonso Rubio-NavarroRenal, Vascular and Diabetes Research Lab, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
Victor Farré-AlinsMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
Paloma Narros-FernandezMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
Melania Guerrero-HueRenal, Vascular and Diabetes Research Lab, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
Juan Antonio MorenoRenal, Vascular and Diabetes Research Lab, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
Juliana M RosaMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.
José M RodaServicio de Neurocirugía, Hospital Universitario La Paz, Madrid, Spain.
Borja J Hernández-GarcíaServicio de Neurocirugía, Hospital Universitario La Paz, Madrid, Spain.
Javier EgeaMolecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain.ORCID 0000-0003-4704-3019
Hospital Universitario Santa Cristina · ESHospital Universitario Fundación Jiménez Díaz · ESHospital Universitario La Paz · ESMaastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeIschaemic stroke is a leading cause of death, disability, and a high unmet medical need. Post-reperfusion inflammation and an up-regulation of toll-like receptor 4 (TLR4), an upstream sensor of innate immunity, are associated with poor outcome in stroke patients. Here, we identified the therapeutic effect of targeting the LPS/TLR4 signal transduction pathway. EXPERIMENTAL APPROACH: We tested the effect of the TLR4 inhibitor, eritoran (E5564) in different in vitro ischaemia-related models: human organotypic cortex culture, rat organotypic hippocampal cultures, and primary mixed glia cultures. We explored the therapeutic window of E5564 in the transient middle cerebral artery occlusion model of cerebral ischaemia in mice. KEY

resultsIn vivo, administration of E5564 1 and 4 hr post-ischaemia reduced the expression of different pro-inflammatory chemokines and cytokines, infarct volume, blood-brain barrier breakdown, and improved neuromotor function, an important clinically relevant outcome. In the human organotypic cortex culture, E5564 reduced the activation of microglia and ROS production evoked by LPS. CONCLUSION AND IMPLICATIONS: TLR4 signalling has a causal role in the inflammation associated with a poor post-stroke outcome. Importantly, its inhibition by eritoran (E5564) provides neuroprotection both in vitro and in vivo, including in human tissue, suggesting a promising new therapeutic approach for ischaemic stroke.

Indexed as

AnimalsAnti-Inflammatory AgentsBrainBrain IschemiaCell LineCytokinesDisease Models, AnimalFemaleHumansLipid AMaleMice, Inbred C57BLMicrogliaNeuroprotective AgentsPhenotypeRats, Sprague-DawleyAnti-Inflammatory AgentsCytokinesE5564Lipid ANeuroprotective AgentsReactive Oxygen SpeciesToll-Like Receptor 4

Identifiers

PMID31074003
PMCPMC6609554
OpenAlexW2944570962

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.