Evidence map›Paper›PMID 31865791›Full record

ArticleHypertension (Dallas, Tex. : 1979)2020

TLR4 (Toll-Like Receptor 4) Mediates the Development of Intracranial Aneurysm Rupture.

Kazuha Mitsui, Taichi Ikedo, Yoshinobu Kamio, Hajime Furukawa, Michael T Lawton, Tomoki Hashimoto

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 2 pooled it
4.2field-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

28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Molecular Targets for Intracranial Aneurysm Treatment.International journal of molecular sciences · 2025
    Review
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  11. Peripheral macrophages in the development and progression of structural cerebrovascular pathologies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Review
  12. Article
  13. Integrative analysis of multi-omics data to identify three immune-related genes in the formation and progression of intracranial aneurysms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
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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

6 authors at 1 institution in 1 country.

Kazuha MitsuiFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Taichi IkedoFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Yoshinobu KamioFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Hajime FurukawaFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Michael T LawtonFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Tomoki HashimotoFrom the Department of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Barrow Neurological Institute · US

Funding

EGF-ADAM17 axis in the pathophysiology of intracranial aneurysmR01NS109382 · NINDS · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI EGUCHI, SATORU, HASHIMOTO, TOMOKI · 2019 to 2023
$2.2M
Mechanisms for intracranial aneurysm ruptureR01NS109584 · NINDS · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI HASHIMOTO, TOMOKI · 2020 to 2024
$1.9M
The Role of Mast Cells in the Pathophysiology of Intracranial AneurysmR01NS082280 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HASHIMOTO, TOMOKI · 2013 to 2017
$1.7M
NINDS NIH HHS R01 NS082280NINDS NIH HHS R01 NS109382NINDS NIH HHS R01 NS109584
6 · The paper itself

Abstract

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

Indexed as

Gene Expression RegulationAneurysm, RupturedAnimalsCytokinesDisease Models, AnimalIntracranial AneurysmMaleMiceMice, Inbred C57BLMice, KnockoutRNAToll-Like Receptor 4CytokinesRNAToll-Like Receptor 4intracranial aneurysmintracranial hemorrhagestrokesubarachnoid hemorrhagetoll-like receptor 4

Identifiers

PMID31865791
PMCPMC7377296
OpenAlexW2997349768

What OpenQuestion holds

Textmetadata
LicenceTDM
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.