Evidence map›Paper›PMID 34952601›Full record

ArticleJournal of neuroinflammation2021

Pericytes as mediators of infiltration of macrophages in multiple sclerosis.

Deepak Kumar Kaushik, Anindita Bhattacharya, Brian Mark Lozinski, V Wee Yong

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

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 52 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

4 authors at 2 institutions in 1 country.

Deepak Kumar KaushikHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB, T2N 4N1, Canada. dkaushik@mun.ca.
Anindita BhattacharyaHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB, T2N 4N1, Canada.
Brian Mark LozinskiHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB, T2N 4N1, Canada.
V Wee YongHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB, T2N 4N1, Canada. vyong@ucalgary.ca.ORCID http://orcid.org/0000-0002-2600-3563
University of Calgary · CAMemorial University of Newfoundland · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMultiple sclerosis (MS) is a neurodegenerative condition of the central nervous system (CNS). It is associated with blood-brain barrier (BBB) breakdown and intravasation of leukocytes, particularly monocyte-derived macrophages, into the CNS. Pericytes are mural cells that are encased within the basement membrane of vasculature, and they contribute functionally to the neurovascular unit. These cells play an important role in maintaining BBB integrity and CNS homeostasis. However, the critical role of pericytes in mediating inflammation in MS or its models is unclear. Whether pericytes infiltrate into the CNS parenchyma in MS also needs clarification.

methodsCNS samples from the experimental autoimmune encephalomyelitis (EAE) mouse model of MS were collected at different time points for immunohistochemical analysis of pericytes along the inflamed vasculature. These findings were validated using MS brain specimens, and further analysis of pericyte involvement in inflammation was carried out by culturing primary pericytes and macrophages. Multiplex ELISA, transmigration assay and real-time PCR were used to study the inflammatory potential of pericytes in cultures.

resultsWe found that pericytes exhibit a heterogenous morphology, with notable elongation in the inflamed perivascular cuffs of EAE. This was manifested by a decrease in pericyte density but an increase in the coverage by pericytes along the vasculature. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix proteins enriched within inflamed perivascular cuffs, elevated levels of pro-inflammatory chemokines/cytokines in pericytes in culture. Importantly, pericytes stimulated with CSPGs enhanced macrophage migration. We did not detect pericytes in the CNS parenchyma during EAE, and this was corroborated in MS brain samples.

conclusionsOur data suggest that pericytes seek to restore the BBB through increased coverage, but that their exposure to CSPGs prompt their facilitation of macrophages to enter the CNS to elevate neuroinflammation in EAE and MS.

Indexed as

AnimalsBlood-Brain BarrierBrainChemokinesCytokinesEncephalitisEncephalomyelitis, Autoimmune, ExperimentalFemaleImmunohistochemistryMacrophagesMiceMice, Inbred C57BLMultiple SclerosisPericytesPrimary Cell CultureChemokinesCytokinesBrainCSPGsInflammationMacrophageMultiple sclerosisPericyte

Identifiers

PMID34952601
PMCPMC8705458
OpenAlexW4200624489

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.