Evidence map›Paper›PMID 38158246›Full record

ArticleUltrasound in medicine & biology2024

Development of an In Vitro Model to Study Mechanisms of Ultrasound-Targeted Microbubble Cavitation-Mediated Blood-Brain Barrier Opening.

Grace E Conway, Anurag N Paranjape, Xucai Chen, Flordeliza S Villanueva

Open access · greenAbstract read
In one paragraph

Article in Ultrasound in medicine & biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Grace E ConwayCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Medical Scientist Training Program, University of Pittsburgh, Pittsburgh, PA, USA.
Anurag N ParanjapeCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Xucai ChenCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Flordeliza S VillanuevaCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: villanuevafs@upmc.edu.
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Biological and Physical Mechanisms of ultrasound/microbubble-mediated therapeutic gene delivery across the endothelial barrierR01EB026966 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VILLANUEVA, FLORDELIZA S · 2018 to 2021
$3.0M
Treatment of Alzheimer’s Disease using Ultrasound-Targeted Microbubble Cavitation-Mediated Blood Brain Barrier Opening to Facilitate Drug Delivery to the BrainF30AG077800 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CONWAY, GRACE · 2022 to 2025
$213k
NCI NIH HHS P30 CA047904NIA NIH HHS F30 AG077800NIBIB NIH HHS R01 EB026966
6 · The paper itself

Abstract

objectiveUltrasound-targeted microbubble cavitation (UTMC)-mediated blood-brain barrier (BBB) opening is being explored as a method to increase drug delivery to the brain. This strategy has progressed to clinical trials for various neurological disorders, but the underlying cellular mechanisms are incompletely understood. In the study described here, a contact co-culture transwell model of the BBB was developed that can be used to determine the signaling cascade leading to increased BBB permeability.

methodsThis BBB model consists of bEnd.3 cells and C8-D1A astrocytes seeded on opposite sides of a transwell membrane. Pulsed ultrasound (US) is applied to lipid microbubbles (MBs), and the change in barrier permeability is measured via transendothelial electrical resistance and dextran flux. Live cell calcium imaging (Fluo-4 AM) is performed during UTMC treatment.

resultsThis model exhibits important features of the BBB, including endothelial tight junctions, and is more restrictive than the endothelial cell (EC) monolayer alone. When US is applied to MBs in contact with the ECs, BBB permeability increases in this model by two mechanisms: UTMC induces pore formation in the EC membrane (sonoporation), leading to increased transcellular permeability, and UTMC causes formation of reversible inter-endothelial gaps, which increases paracellular permeability. Additionally, this study determines that calcium influx into ECs mediates the increase in BBB permeability after UTMC in this model.

conclusionBoth transcellular and paracellular permeability can be used to increase drug delivery to the brain. Future studies can use this model to determine how UTMC-induced calcium-mediated signaling increases BBB permeability.

Indexed as

Blood-Brain BarrierMicrobubblesAnimalsBrainCalciumEndothelial CellsMiceCalciumBlood–brain barrierContrast agentMicrobubbleSonoporationUltrasound

Identifiers

PMID38158246
PMCPMC10843834
OpenAlexW4390399008

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.