Evidence map›Paper›PMID 31303172›Full record

ArticleFluids and barriers of the CNS2019

The role of mutations associated with familial neurodegenerative disorders on blood-brain barrier function in an iPSC model.

Moriah E Katt, Lakyn N Mayo, Shannon E Ellis, Vasiliki Mahairaki, Jeffrey D Rothstein, Linzhao Cheng, Peter C Searson

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

Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.9field-weighted citation impact, top 5% 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, 77 citations in OpenAlex.

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    Review
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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

7 authors at 1 institution in 1 country.

Moriah E KattInstitute for Nanobiotechnology, Johns Hopkins University, 100 Croft Hall, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Lakyn N MayoInstitute for Nanobiotechnology, Johns Hopkins University, 100 Croft Hall, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Shannon E EllisDepartment of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD, USA.
Vasiliki MahairakiDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeffrey D RothsteinDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Linzhao ChengInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, 100 Croft Hall, 3400 North Charles Street, Baltimore, MD, 21218, USA. searson@jhu.edu.ORCID http://orcid.org/0000-0002-5417-0828
Johns Hopkins University · US

Funding

Defense Threat Reduction Agency (US) HDTRA1-15-1-0046
6 · The paper itself

Abstract

backgroundBlood-brain barrier dysfunction is associated with many late-stage neurodegenerative diseases. An emerging question is whether the mutations associated with neurodegenerative diseases can independently lead to blood-brain barrier (BBB) dysfunction. Studies from patient-derived induced pluripotent stem cells suggest that mutations associated with neurodegenerative disease are non-cell autonomous, resulting in gain of toxic function in derived neurons and astrocytes. Here we assess whether selected mutations associated with neurodegenerative diseases can contribute to impairment of the blood-brain barrier.

methodsWe assessed barrier function of confluent monolayers of human brain microvascular endothelial cells (hBMECs) derived from induced pluripotent stem cells (iPSC) from three healthy individuals and eight individuals with neurodegenerative disease. We systematically assessed protein and gene expression of BBB biomarkers, transendothelial resistance (TEER), permeability of Lucifer yellow, permeability of D-glucose, permeability of rhodamine 123, the efflux ratio of rhodamine 123, and P-gp inhibition using Tariquidar for confluent monolayers of human brain microvascular endothelial cell (hBMECs).

resultsWe provide evidence supporting the hypothesis that mutations associated with neurodegenerative disease can independently cause BBB dysfunction. These functional changes are not catastrophic since barrier breakdown would result in BBB impairment during development. Synergistic interactions between non-cell autonomous cerebrovascular dysfunction and the effects of gain-of-toxic function in neurons (e.g. toxic oligomers) are likely to increase disease burden through a positive feedback mechanism.

conclusionsThese results suggest that the accumulation of defects in brain microvascular endothelial cells may ultimately lead to impairment of the BBB. Small changes in barrier function over time could lead to accumulated defects that result in positive feedback to unrelated central nervous system diseases.

Indexed as

AdultAgedBlood-Brain BarrierEndothelial CellsFemaleHumansInduced Pluripotent Stem CellsMaleMiddle AgedMutationNeurodegenerative DiseasesBlood–brain barrierDifferentiationHuman brain microvascular endothelial cellsInduced pluripotent stem cellsNeurodegenerative disease

Identifiers

PMID31303172
PMCPMC6628493
OpenAlexW2959450640

What OpenQuestion holds

Textmetadata
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.