Evidence map›Paper›PMID 31030181›Full record

ArticleiScience2019

Clostridium perfringens Epsilon Toxin Compromises the Blood-Brain Barrier in a Humanized Zebrafish Model.

Drew Adler, Jennifer R Linden, Samantha V Shetty, Yinghua Ma, Monika Bokori-Brown, Richard W Titball, Timothy Vartanian

Open access · goldAbstract read
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.5field-weighted citation impact, top 31% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Epsilon Toxin fromToxins · 2024
    Article
  5. Article
  6. Article
  7. Review
  8. Toxins · 2023
    Article
  9. Article
  10. Article
  11. Interaction ofToxins · 2022
    Article
  12. Article
  13. Article
  14. Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers.International journal of molecular sciences · 2021
    Review
  15. Review
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 2 institutions in 2 countries.

Drew AdlerBrain and Mind Research Institute, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA; Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14850, USA.
Jennifer R LindenBrain and Mind Research Institute, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
Samantha V ShettyBrain and Mind Research Institute, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
Yinghua MaBrain and Mind Research Institute, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
Monika Bokori-BrownDepartment of Biosciences, University of Exeter, Exeter, Devon EX4 4SB, UK.
Richard W TitballDepartment of Biosciences, University of Exeter, Exeter, Devon EX4 4SB, UK.
Timothy VartanianBrain and Mind Research Institute, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. Electronic address: tiv2002@med.cornell.edu.
Cornell University · USUniversity of Exeter · GB

Funding

Damage Associated Molecular Patterns and Regenerative Failure in MSR01NS104350 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI VARTANIAN, TIMOTHY · 2018 to 2022
$1.8M
Functional Link Between Innate Immunity, Oligodendrocyte Development, and MyelinaR01NS066007 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI VARTANIAN, TIMOTHY · 2009 to 2010
$592k
NINDS NIH HHS R01 NS066007NINDS NIH HHS R01 NS104350
6 · The paper itself

Abstract

Clostridium perfringens epsilon toxin (ETX) is hypothesized to mediate blood-brain barrier (BBB) permeability by binding to the myelin and lymphocyte protein (MAL) on the luminal surface of endothelial cells (ECs). However, the kinetics of this interaction and a general understanding of ETX's behavior in a live organism have yet to be appreciated. Here we investigate ETX binding and BBB breakdown in living Danio rerio (zebrafish). Wild-type zebrafish ECs do not bind ETX. When zebrafish ECs are engineered to express human MAL (hMAL), proETX binding occurs in a time-dependent manner. Injection of activated toxin in hMAL zebrafish initiates BBB leakage, hMAL downregulation, blood vessel stenosis, perivascular edema, and blood stasis. We propose a kinetic model of MAL-dependent ETX binding and neurovascular pathology. By generating a humanized zebrafish BBB model, this study contributes to our understanding of ETX-induced BBB permeability and strengthens the proposal that MAL is the ETX receptor.

Indexed as

Model OrganismMolecular Mechanism of BehaviorPathogenic OrganismVascular Remodeling

Identifiers

PMID31030181
PMCPMC6487375
OpenAlexW2937890620

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.