Evidence map›Paper›PMID 35789221›Full record

ArticlePloS one2022

Astrocytes and pericytes attenuate severely injured patient plasma mediated expression of tight junction proteins in endothelial cells.

Preston Stafford, Sanchayita Mitra, Margot Debot, Patrick Lutz, Arthur Stem, Jamie Hadley, Patrick Hom, Terry R Schaid, Mitchell J Cohen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

6 citing papers in PubMed, 9 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

9 authors at 1 institution in 1 country.

Preston StaffordDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0003-4848-9979
Sanchayita MitraDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Margot DebotDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Patrick LutzDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Arthur StemDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-2807-0655
Jamie HadleyDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0001-8965-0269
Patrick HomDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Terry R SchaidDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0001-7183-0771
Mitchell J CohenDivision of GITES, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0003-1402-5869
University of Colorado Anschutz Medical Campus · US

Funding

Analysis and Characterization of Trauma-Induced CoagulopathyUM1HL120877 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MORRISSEY, JAMES H., WISNIEWSKI, STEPHEN R · 2013 to 2019
$26.6M
HSRD VA CDA 13-025NHLBI NIH HHS UM1 HL120877
6 · The paper itself

Abstract

Blood Brain Barrier (BBB) breakdown is a secondary form of brain injury which has yet to be fully elucidated mechanistically. Existing research suggests that breakdown of tight junction proteins between endothelial cells is a primary driver of increased BBB permeability following injury, and intercellular signaling between primary cells of the neurovascular unit: endothelial cells, astrocytes, and pericytes; contribute to tight junction restoration. To expound upon this body of research, we analyzed the effects of severely injured patient plasma on each of the cell types in monoculture and together in a triculture model for the transcriptional and translational expression of the tight junction proteins Claudins 3 and 5, (CLDN3, CLDN5) and Zona Occludens 1 (ZO-1). Conditioned media transfer studies were performed to illuminate the cell type responsible for differential tight junction expression. Our data show that incubation with 5% human ex vivo severely injured patient plasma is sufficient to produce a differential response in endothelial cell tight junction mRNA and protein expression. Endothelial cells in monoculture produced a significant increase of CLDN3 and CLDN5 mRNA expression, (3.98 and 3.51 fold increase vs. control respectively, p<0.01) and CLDN5 protein expression, (2.58 fold change vs. control, p<0.01), whereas in triculture, this increase was attenuated. Our triculture model and conditioned media experiments suggest that conditioned media from astrocytes and pericytes and a triculture of astrocytes, pericytes and endothelial cells are sufficient in attenuating the transcriptional increases of tight junction proteins CLDN3 and CLDN5 observed in endothelial monocultures following incubation with severely injured trauma plasma. This data suggests that inhibitory molecular signals from astrocytes and pericytes contributes to prolonged BBB breakdown following injury via tight junction transcriptional and translational downregulation of CLDN5.

Indexed as

AstrocytesPericytesCulture Media, ConditionedEndothelial CellsHumansRNA, MessengerTight Junction ProteinsCulture Media, ConditionedRNA, MessengerTight Junction Proteins

Identifiers

PMID35789221
PMCPMC9255734
OpenAlexW4284712038

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.