Evidence map›Paper›PMID 38114994›Full record

ArticleFluids and barriers of the CNS2023

Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood - brain barrier function.

Baharak Hosseinkhani, Gayel Duran, Cindy Hoeks, Doryssa Hermans, Melissa Schepers, Paulien Baeten, Joren Poelmans, Britt Coenen, Kübra Bekar, Isabel Pintelon and 5 more

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 18 citations in OpenAlex.

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  8. The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  13. Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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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

15 authors at 4 institutions in 2 countries.

Baharak Hosseinkhani *University MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Gayel Duran *University MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Cindy HoeksUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Doryssa HermansUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Melissa SchepersUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Paulien BaetenUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Joren PoelmansUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Britt CoenenUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Kübra BekarUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Isabel PintelonLaboratory of Cell Biology & Histology/Antwerp Centre for Advanced Microscopy (ACAM), University of Antwerp, Universiteitsplein 1, Antwerp, 2610, Belgium.
Jean-Pierre TimmermansLaboratory of Cell Biology & Histology/Antwerp Centre for Advanced Microscopy (ACAM), University of Antwerp, Universiteitsplein 1, Antwerp, 2610, Belgium.
Tim VanmierloUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Luc MichielsBionanotechnology group, Biomedical Research Institute, UHasselt, Diepenbeek, Belgium.
Niels HellingsUniversity MS Center, Campus Diepenbeek, Diepenbeek, Belgium.
Bieke Broux *University MS Center, Campus Diepenbeek, Diepenbeek, Belgium. bieke.broux@uhasselt.be.
Hasselt University · BENational MS Center MelsbroekUniversity of Antwerp · BEMaastricht University · NL

Funding

Fonds Wetenschappelijk Onderzoek 1S87418NFonds Wetenschappelijk Onderzoek G097318Universiteit Hasselt 19DOC18BOFUniversiteit Hasselt 20DOC13BOF
6 · The paper itself

Abstract

Autoreactive T lymphocytes crossing the blood-brain barrier (BBB) into the central nervous system (CNS) play a crucial role in the initiation of demyelination and neurodegeneration in multiple sclerosis (MS). Recently, extracellular vesicles (EV) secreted by BBB endothelial cells (BBB-EC) have emerged as a unique form of cell-to-cell communication that contributes to cerebrovascular dysfunction. However, the precise impact of different size-based subpopulations of BBB-EC-derived EV (BBB-EV) on the early stages of MS remains unclear. Therefore, our objective was to investigate the content and function of distinct BBB-EV subpopulations in regulating BBB integrity and their role in T cell transendothelial migration, both in vitro and in vivo. Our study reveals that BBB-ECs release two distinct size based EV populations, namely small EV (sEV; 30-150 nm) and large EV (lEV; 150-300 nm), with a significantly higher secretion of sEV during inflammation. Notably, the expression patterns of cytokines and adhesion markers differ significantly between these BBB-EV subsets, indicating specific functional differences in the regulation of T cell migration. Through in vitro experiments, we demonstrate that lEV, which predominantly reflect their cellular source, play a major role in BBB integrity loss and the enhanced migration of pro-inflammatory Th1 and Th17.1 cells. Conversely, sEV appear to protect BBB function by inducing an anti-inflammatory phenotype in BBB-EC. These findings align with our in vivo data, where the administration of sEV to mice with experimental autoimmune encephalomyelitis (EAE) results in lower disease severity compared to the administration of lEV, which exacerbates disease symptoms. In conclusion, our study highlights the distinct and opposing effects of BBB-EV subpopulations on the BBB, both in vitro and in vivo. These findings underscore the need for further investigation into the diagnostic and therapeutic potential of BBB-EV in the context of MS.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalExtracellular VesiclesMultiple SclerosisAnimalsBlood-Brain BarrierCentral Nervous SystemEndothelial CellsMiceBBBEVMultiple sclerosis

Identifiers

PMID38114994
PMCPMC10729529
OpenAlexW4389942464

What Socratic 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 Socratic graph.