Evidence map›Paper›PMID 30822467›Full record

ArticleBrain, behavior, and immunity2019

Choroid plexus transcriptome and ultrastructure analysis reveals a TLR2-specific chemotaxis signature and cytoskeleton remodeling in leukocyte trafficking.

Amin Mottahedin, C Joakim Ek, Katarina Truvé, Henrik Hagberg, Carina Mallard

Open access · greenAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

35 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  8. The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
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  14. Paclitaxel triggers molecular and cellular changes in the choroid plexus.Frontiers in pain research (Lausanne, Switzerland) · 2024
    Article
  15. Article
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  18. Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Review
  19. Article
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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

5 authors at 2 institutions in 2 countries.

Amin MottahedinCentre of Perinatal Medicine and Health, Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
C Joakim EkCentre of Perinatal Medicine and Health, Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Katarina TruvéBioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Henrik HagbergCentre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK; Centre of Perinatal Medicine and Health, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Carina MallardCentre of Perinatal Medicine and Health, Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: carina.mallard@neuro.gu.se.
University of Gothenburg · SESt Thomas' Hospital · GB

Funding

SENSITIVE AND SELECTIVE DETECTION OF PEPTIDESR01GM044842 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEBER, STEPHEN G. · 1991 to 2018
$4.9M
Perinatal stroke: effects of bioactive lipids on immune-neurovascular axis and brain repairR01HL139685 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VEXLER, ZINAIDA S · 2018 to 2021
$2.1M
NHLBI NIH HHS R01 HL139685NIGMS NIH HHS R01 GM044842
6 · The paper itself

Abstract

Perinatal infection and inflammation are major risk factors for injury in the developing brain, however, underlying mechanisms are not fully understood. Leukocyte migration to the cerebrospinal fluid (CSF) and brain is a hallmark of many pathologies of the central nervous system including those in neonates. We previously reported that systemic activation of Toll-like receptor (TLR) 2, a major receptor for gram-positive bacteria, by agonist Pam3CSK4 (P3C) resulted in dramatic neutrophil and monocyte infiltration to the CSF and periventricular brain of neonatal mice, an effect that was absent by the TLR4 agonist, LPS. Here we first report that choroid plexus is a route of TLR2-mediated leukocyte infiltration to the CSF by performing flow cytometry and transmission electron microscopy (TEM) of the choroid plexus. Next, we exploited the striking discrepancy between P3C and LPS effects on cell migration to determine the pathways regulating leukocyte trafficking through the choroid plexus. We performed RNA sequencing on the choroid plexus after administration of P3C and LPS to postnatal day 8 mice. A cluster gene analysis revealed a TLR2-specific signature of chemotaxis represented by 80-fold increased expression of the gene Ccl3 and 1000-fold increased expression of the gene Cxcl2. Ingenuity pathway analysis (IPA) revealed TLR2-specific molecular signaling related to cytoskeleton organization (e.g. actin signaling) as well as inositol phospholipids biosynthesis and degradation. This included upregulation of genes such as Rac2 and Micall2. In support of IPA results, ultrastructural analysis by TEM revealed clefting and perforations in the basement membrane of the choroid plexus epithelial cells in P3C-treated mice. In summary, we show that the choroid plexus is a route of TLR2-mediated transmigration of neutrophils and monocytes to the developing brain, and reveal previously unrecognized mechanisms that includes a specific chemotaxis profile as well as pathways regulating cytoskeleton and basement membrane remodeling.

Indexed as

AnimalsAnimals, NewbornBrainCell MovementCentral Nervous SystemChemotaxisChoroid PlexusCytoskeletonFlow CytometryInflammationLeukocytesMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionMonocytesNeutrophilsTlr2 protein, mouseToll-Like Receptor 2Basement membraneChoroid plexusCytoskeletonInfectionInflammationInositolLeukocyte migrationMicall2RemodelingToll-like receptor

Identifiers

PMID30822467
PMCPMC6591031
OpenAlexW2916519553

What OpenQuestion holds

Textmetadata
LicenceTDM
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.