Evidence map›Paper›PMID 33133680›Full record

ArticleJournal of advanced research2020

TRPV4 promotes acoustic wave-mediated BBB opening via Ca

Wei-Hao Liao, Ming-Yen Hsiao, Yi Kung, Hao-Li Liu, Jean-Christophe Béra, Claude Inserra, Wen-Shiang Chen

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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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

7 authors at 5 institutions in 2 countries.

Wei-Hao LiaoDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Ming-Yen HsiaoDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Yi KungDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hao-Li LiuDepartment of Electrical Engineering, Chang Gung University, Taoyuan, Taiwan.
Jean-Christophe BéraLabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, F-69003 Lyon, France.
Claude InserraLabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, F-69003 Lyon, France.
Wen-Shiang ChenDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
National Taiwan University Hospital · TWUniversité Claude Bernard Lyon 1 · FRChang Gung University · TWNational Health Research Institutes · TWNational Taiwan University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionNumerous studies have shown the ability of low-energy acoustic waves such as focused ultrasound or shockwave to transiently open blood-brain barrier (BBB) and facilitate drug delivery to the brain. Preclinical and clinical evidences have well demonstrated the efficacy and safety in treating various brain disorders. However, the molecular mechanisms of acoustic waves on the BBB are still not fully understood.

objectivesThe present study aimed at exploring the possible molecular mechanisms of acoustic wave stimulation on brains. METHODS BRIEFLY DESCRIBE THE EXPERIMENTAL

designThe left hemisphere of the rat's brain was treated with pulsed ultrasound from a commercial focused shockwave or a planar ultrasound device, and the right hemisphere served as a control. One hour after the mechanical wave stimulation or overnight, the rats were sacrificed and the brains were harvested for protein or histological analysis. Agonists and antagonists related to the signal transduction pathways of tight junction proteins were used to investigate the possible intracellular mechanisms.

resultsIntracellular signal transduction analysis shows calcium influx through transient receptor potential vanilloid 4 (TRPV4) channels, and the activation of PKC-δ pathway to mediate dissociation of ZO-1 and occludin after acoustic wave stimulation. The activation of TRPV4 or PKC-δ signaling further increased the expression level of TRPV4, suggesting a feedback loop to regulate BBB permeability. Moreover, the tight junction proteins dissociation can be reversed by administration of PKC-δ inhibitor and TRPV4 antagonist.

conclusionThe present study shows the crucial role of TRPV4 in acoustic wave-mediated BBB permeability, specifically its effect on compromising tight junction proteins, ZO-1 and occludin. Our findings provide a new molecular perspective to explain acoustic wave-mediated BBB opening. Moreover, activation of TRPV4 by agonists may reduce the threshold intensity level of acoustic waves for BBB opening, which may prevent undesirable mechanical damages while maintaining efficient BBB opening.

Indexed as

Acoustic wavesBlood–brain barrierPKC-δShockwaveTRPV4Ultrasound

Identifiers

PMID33133680
PMCPMC7584681
OpenAlexW3036506251

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.