Evidence map›Paper›PMID 31697040›Full record

ArticleCNS neuroscience & therapeutics2019

Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain.

Wenting Zhang, Jingyan Zhao, Rongrong Wang, Ming Jiang, Qing Ye, Amanda D Smith, Jun Chen, Yejie Shi

Open access · goldAbstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

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  7. Monocyte-derived macrophages and their roles in ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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33 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Wenting ZhangDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Jingyan ZhaoDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Rongrong WangDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Ming JiangDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Qing YeDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Amanda D SmithDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Jun ChenDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.
Yejie ShiDepartment of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-7502-9201
University of Pittsburgh · US

Funding

American Heart Association-American Stroke Association 17SDG33630130
6 · The paper itself

Abstract

aimsBlood-borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain.

methodsWe performed whole-genome RNA sequencing on the monocyte/macrophage population sorted from mouse brain and peripheral blood 5 days after permanent focal cerebral ischemia. In addition, the spatial and temporal profiles of macrophage efferocytosis were examined in vivo by immunohistochemistry 3-7 days after brain ischemia.

resultsRobust transcriptomic changes occurred in monocytes/macrophages upon infiltrating the poststroke brain. Functional enrichment analysis revealed a transcriptome of brain macrophages that strongly favored efferocytic activity. A large number of efferocytosis-related genes were upregulated in brain macrophages, the products of which are essential components involved in various steps of efferocytosis, such as chemotaxis, recognition of dead cells, engulfment, and processing of phagosomes. The efferocytic activity of brain macrophages were verified by immunohistochemistry, wherein Iba1-labeled microglia/macrophages effectively cleared apoptotic neurons in the infarct during the subacute stage after brain ischemia. We also identified PPARγ and STAT6 as potential upstream regulators that shaped this proefferocytic and inflammation-resolving transcriptome of macrophages in the poststroke brain.

conclusionMacrophages play a crucial role in the phagocytic clearance of dead neurons after ischemic stroke and promote the resolution of inflammation in the brain. Molecular therapies that enhance macrophage efferocytic capability may be promising treatments for ischemic stroke by facilitating inflammation resolution, brain repair, and recovery of neurological functions.

Indexed as

AnimalsApoptosisBrainBrain IschemiaImmunohistochemistryInflammationMacrophagesMaleMiceMice, Inbred C57BLMonocytesNeuroimagingPhagocytosisPPAR gammaSequence Analysis, RNASTAT6 Transcription FactorPPAR gammaStat6 protein, mouseSTAT6 Transcription Factorapoptotic cell clearancefocal cerebral ischemiainflammation resolutionphagocytosisRNA-seq

Identifiers

PMID31697040
PMCPMC6887920
OpenAlexW2987577889

What OpenQuestion holds

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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.