Evidence map›Paper›PMID 30639264›Full record

ArticleNeurochemistry international2019

Developmental differences in microglia morphology and gene expression during normal brain development and in response to hypoxia-ischemia.

Pelin Cengiz, Dila Zafer, Jayadevi H Chandrashekhar, Vishal Chanana, Jacob Bogost, Alex Waldman, Becca Novak, Douglas B Kintner, Peter A Ferrazzano

Open access · greenAbstract read
In one paragraph

Article in Neurochemistry international, 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
2.8field-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

35 citing papers in PubMed, 55 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 2 institutions in 1 country.

Pelin CengizDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: cengiz@wisc.edu.
Dila ZaferWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Jayadevi H ChandrashekharWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; University of Illinois at Urbana-Champaign, IL, USA.
Vishal ChananaWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Jacob BogostWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Alex WaldmanWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Emory University School of Medicine, Atlanta, GA, USA.
Becca NovakWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Douglas B KintnerWaisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Peter A FerrazzanoDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
University of Wisconsin–Madison · USUniversity of Illinois Urbana-Champaign · US

Funding

WISCONSIN CENTER ON MENTAL RETARDATION: CORE SUPPORTP30HD003352 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI MAILICK, MARSHA RUTH · 1985 to 2015
$25.2M
Waisman Intellectual and Developmental Disabilities Research Center Down Syndrome RegistryU54HD090256 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI CHANG, QIANG · 2016 to 2020
$6.0M
Estrogen receptors and TrkB mediated neuroprotection in neonatal hypoxia-ischemiaK08NS088563 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI CENGIZ, PELIN · 2015 to 2019
$994k
Age-dependent microglial responses in hypoxia-ischemiaK08NS078113 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI FERRAZZANO, PETER A · 2013 to 2017
$967k
NICHD NIH HHS P30 HD003352NICHD NIH HHS U54 HD090256NINDS NIH HHS K08 NS078113NINDS NIH HHS K08 NS088563
6 · The paper itself

Abstract

backgroundNeuroinflammation plays an important role in ischemic brain injury and recovery, however the interplay between brain development and the neuroinflammatory response is poorly understood. We previously described age-dependent differences in the microglial response and the effect of microglial inhibition. Here we investigate whether age-dependent microglial responses may be related to pre-injury developmental differences in microglial phenotype.

methodsMeasures of microglia morphology were quantified using semi-automated software analysis of immunostained sections from postnatal day 2 (P2), P9, P30 and P60 mice using IMARIS. Microglia were isolated from P2, P9, P30 and P60 mice, and expression of markers of classical and alternative microglial activation was assessed, as well as transforming growth factor beta (TGF-β) receptor, Serpine1, Mer Tyrosine Kinase (MerTK), and the suppressor of cytokine signaling (SOCS3). Hypoxia-ischemia (HI) was induced in P9 and P30 mice using unilateral carotid artery ligation and exposure to 10% oxygen for 50 min. Microglia morphology and microglial expression of genes in the TGF-β and MerTK pathways were determined in ipsilateral and contralateral hippocampus.

resultsA progressive and significant increase in microglia branching morphology was seen in all brain regions from P2 to P30. No consistent classical or alternative activation profile was seen in isolated microglia. A clear transition to increased expression of TGF-β and its downstream effector serpine1 was seen between P9 and P30. A similar increase in expression was seen in MerTK and its downstream effector SOCS3. HI resulted in a significant decrease in branching morphology only in the P9 mice, and expression of TGF-β receptor, Serpine1, MerTK, and SOCS3 were elevated in P30 mice compared to P9 post-HI.

conclusionMicroglia maturation is associated with changes in morphology and gene expression, and microglial responses to ischemia in the developing brain differ based on the age at which injury occurs.

Indexed as

AnimalsAnimals, NewbornBrainCell ShapeDisease Models, AnimalGene ExpressionHippocampusHypoxiaHypoxia-Ischemia, BrainInflammationMice, Inbred C57BLMicrogliaBrain developmentHypoxia-ischemiaMicrogliaPediatrics

Identifiers

PMID30639264
PMCPMC7285704
OpenAlexW2910136779

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.