Evidence map›Paper›PMID 34027087›Full record

ArticleBioengineering & translational medicine2021

Transcriptomic response of brain tissue to focused ultrasound-mediated blood-brain barrier disruption depends strongly on anesthesia.

Alexander S Mathew, Catherine M Gorick, E Andrew Thim, William J Garrison, Alexander L Klibanov, G Wilson Miller, Natasha D Sheybani, Richard J Price

Open access · goldAbstract read
In one paragraph

Article in Bioengineering & translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

19 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  6. Review
  7. Barriers to immune cell infiltration in tumors.Journal for immunotherapy of cancer · 2023
    Review
  8. Article
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  14. Article
  15. Review
  16. Review
  17. Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
  18. Article
  19. Article
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

8 authors at 1 institution in 1 country.

Alexander S MathewDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
Catherine M GorickDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.ORCID https://orcid.org/0000-0002-0139-3438
E Andrew ThimDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
William J GarrisonDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
Alexander L KlibanovDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
G Wilson MillerDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
Natasha D SheybaniDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.
Richard J PriceDepartment of Biomedical Engineering University of Virginia Charlottesville Virginia USA.ORCID https://orcid.org/0000-0002-0237-2102
University of Virginia · US

Funding

Immunotherapeutic Nanoparticle Delivery to Melanoma With MR-Guided Focused UltrasoundR01CA197111 · NCI · UNIVERSITY OF VIRGINIA · PI BULLOCK, TIMOTHY N, ENGELHARD, VICTOR H · 2015 to 2019
$2.6M
Innovative systemic gene therapy for treating Parkinson's diseaseR01NS111102 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI PRICE, RICHARD J., SUK, JUNG SOO · 2019 to 2023
$2.6M
MRI-Guided miRNA Nanoparticle Delivery to Glioblastoma With Focused UltrasoundR01EB020147 · NIBIB · UNIVERSITY OF VIRGINIA · PI HANES, JUSTIN S., PRICE, RICHARD J. · 2015 to 2018
$2.4M
Ultrasound-triggered red blood cell drug delivery with photoacoustic trackingR01EB023055 · NIBIB · UNIVERSITY OF VIRGINIA · PI KLIBANOV, ALEXANDER L · 2017 to 2020
$2.3M
Transdisciplinary Big Data Science Training at UVaT32LM012416 · NLM · UNIVERSITY OF VIRGINIA · PI BROWN, DONALD E, LOUGHRAN, THOMAS P. · 2016 to 2020
$1.3M
Endothelial DNA Methylation, Arteriogenic Capacity, and Shear Stress "Set-Point."R21EB024323 · NIBIB · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2017 to 2018
$442k
Leveraging MR-Guided Focused Ultrasound to Potentiate Immunotherapy for GBMR21CA226607 · NCI · UNIVERSITY OF VIRGINIA · PI BULLOCK, TIMOTHY N · 2019 to 2020
$383k
Leveraging Focused Ultrasound to Sensitize Refractory Melanoma to ImmunotherapyF30CA247254 · NCI · UNIVERSITY OF VIRGINIA · PI MATHEW, ALEXANDER SEAN · 2020 to 2022
$138k
Focused Ultrasound and Multifunctional Nanoparticle Vaccines as Adjuvant Strategies for Cancer ImmunotherapyF99CA234954 · NCI · UNIVERSITY OF VIRGINIA · PI SHEYBANI, NATASHA DIBA · 2018 to 2019
$81k
NCI NIH HHS F30 CA247254NCI NIH HHS F99 CA234954NCI NIH HHS R01 CA197111NCI NIH HHS R21 CA226607NIBIB NIH HHS R01 EB020147NIBIB NIH HHS R01 EB023055NIBIB NIH HHS R21 EB024323NINDS NIH HHS R01 NS111102NLM NIH HHS T32 LM012416
6 · The paper itself

Abstract

Focused ultrasound (FUS) mediated blood-brain barrier disruption (BBBD) targets the delivery of systemically-administered therapeutics to the central nervous system. Preclinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS-induced BBBD in mice anesthetized with either isoflurane with medical air (Iso) or ketamine/dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak-negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell-cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS-mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS-BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling.

Indexed as

anesthesiablood–brain barrierfocused ultrasoundRNA sequencing

Identifiers

PMID34027087
PMCPMC8126816
OpenAlexW3098995729

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.