Evidence map›Paper›PMID 24950164›Full record

ArticleAnesthesiology2014

Down-regulation of microRNA-21 is involved in the propofol-induced neurotoxicity observed in human stem cell-derived neurons.

Danielle M Twaroski, Yasheng Yan, Jessica M Olson, Zeljko J Bosnjak, Xiaowen Bai

Open access · bronzeAbstract read
In one paragraph

Article in Anesthesiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 2 countries.

Danielle M TwaroskiFrom the Departments of Physiology and Anesthesiology (D.M.T., J.M.O., Z.J.B.) and the Department of Anesthesiology (Y.Y., X.B.), Medical College of Wisconsin, Milwaukee, Wisconsin.
Yasheng Yan
Jessica M Olson
Zeljko J Bosnjak
Xiaowen Bai
American Society of Anesthesiologists · USMedical College of Wisconsin · US

Funding

Stem Cell CoreP01GM066730 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI DASH, RANJAN K · 2003 to 2019
$23.6M
INTERACTION BETWEEN ANESTHETICS AND CALCIUM ANTAGONISTSR01HL034708 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI BOSNJAK, ZELJKO J. · 1986 to 2013
$3.9M
microRNAs and Anesthetic-Induced Developmental NeurotoxicityR01GM112696 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI BAI, XIAOWEN · 2014 to 2022
$3.0M
NHLBI NIH HHS R01 HL034708NHLBI NIH HHS R01HL034708NIGMS NIH HHS P01 GM066730NIGMS NIH HHS P01GM066730NIGMS NIH HHS R01 GM112696NIGMS NIH HHS R01GM112696
6 · The paper itself

Abstract

backgroundRecent studies in various animal models have suggested that anesthetics such as propofol, when administered early in life, can lead to neurotoxicity. These studies have raised significant safety concerns regarding the use of anesthetics in the pediatric population and highlight the need for a better model to study anesthetic-induced neurotoxicity in humans. Human embryonic stem cells are capable of differentiating into any cell type and represent a promising model to study mechanisms governing anesthetic-induced neurotoxicity.

methodsCell death in human embryonic stem cell-derived neurons was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling staining, and microRNA expression was assessed using quantitative reverse transcription polymerase chain reaction. miR-21 was overexpressed and knocked down using an miR-21 mimic and antagomir, respectively. Sprouty 2 was knocked down using a small interfering RNA, and the expression of the miR-21 targets of interest was assessed by Western blot.

resultsPropofol dose and exposure time dependently induced significant cell death (n = 3) in the neurons and down-regulated several microRNAs, including miR-21. Overexpression of miR-21 and knockdown of Sprouty 2 attenuated the increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells following propofol exposure. In addition, miR-21 knockdown increased the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells by 30% (n = 5). Finally, activated signal transducer and activator of transcription 3 and protein kinase B (Akt) were down-regulated, and Sprouty 2 was up-regulated following propofol exposure (n = 3).

conclusionsThese data suggest that (1) human embryonic stem cell-derived neurons represent a promising in vitro human model for studying anesthetic-induced neurotoxicity, (2) propofol induces cell death in human embryonic stem cell-derived neurons, and (3) the propofol-induced cell death may occur via a signal transducer and activator of transcription 3/miR-21/Sprouty 2-dependent mechanism.

Indexed as

Anesthetics, IntravenousAnimalsCell DifferentiationCoculture TechniquesDose-Response Relationship, DrugDown-RegulationHumansMiceMicroRNAsNeural Stem CellsNeuronsPropofolAnesthetics, IntravenousMicroRNAsMIRN21 microRNA, humanPropofol

Identifiers

PMID24950164
PMCPMC4174986
OpenAlexW2048915618

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.