Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 65

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain

Choi, Ja Yong, Kim, Jong Youl, Kim, Jae Young, Park, Joohyun, Lee, Won Taek, Lee, Jong Eun·2017·Experimental Neurobiology
DOI 10.5607/en.2017.26.1.33PMC PMC5326713
Open this paper in CoChat — free account

Abstract

Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke.Activated microglia promote neuronal damage or protection in injured brain tissue.Extracellular signals polarize the microglia towards the M1/M2 phenotype.The M1/M2 phenotype microglia released pro-and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs).In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs.First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells.Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h.In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotypeconditioned media for 3 d.We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA.The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke.The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media.These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.5607/en.2017.26.1.33

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Polarization of BV2 microglial cells using conditioned media. (A) Schematic time course of the in vitro experiments. (B) Immunohistochemistry of CD68 (M1 phenotype microglia; green) and CD206 (M2 phenotype microglia; red). In BV2 microglial cell, the expression of CD68 significantly increased in M1 conditioned media compared with M2 conditioned media. CD206 is expressed only in M2 conditioned media (Scale bar=20 um, n=5/group).
Fig. 1 Polarization of BV2 microglial cells using conditioned media. (A) Schematic time course of the in vitro experiments. (B) Immunohistochemistry of CD68 (M1 phenotype microglia; green) and CD206 (M2 phenotype microglia; red). In BV2 microglial cell, the expression of CD68 significantly increased in M1 conditioned media compared with M2 conditioned media. CD206 is expressed only in M2 conditioned media (Scale bar=20 um, n=5/group).CC BY-NC · PubMed Central
Fig. 2 Proliferation SVZ-NSPCs in M2 conditioned media. (A) Schematic time course of the in vivo and ex vivo experiments. (B) Immunohistochemistry of Ki67 and BrdU in M0, M1, and M2 conditioned media shows the proliferation of SVZ-NSPCs in THE organotypic brain. (C) Quantification graph of the ratio of Ki67+ and BrdU+ cells of SVZ-NSPCs in organotypic brain (Scale bar=20 um, **p<0.05 vs. M0 conditioned media, n=5/group).
Fig. 2 Proliferation SVZ-NSPCs in M2 conditioned media. (A) Schematic time course of the in vivo and ex vivo experiments. (B) Immunohistochemistry of Ki67 and BrdU in M0, M1, and M2 conditioned media shows the proliferation of SVZ-NSPCs in THE organotypic brain. (C) Quantification graph of the ratio of Ki67+ and BrdU+ cells of SVZ-NSPCs in organotypic brain (Scale bar=20 um, **p<0.05 vs. M0 conditioned media, n=5/group).CC BY-NC · PubMed Central
Fig. 3 Differentiation of SVZ-NSPCs in M2 conditioned media. M0, M1, or M2 conditioned media induced the differentiation of SVZ-NSPCs in the organotypic brain. (A and B) Immunohistochemistry and quantification graph of the ratio of DCX+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (C and D) Immunohistochemistry and quantification graph of the ratio of NeuN+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (E and F) Immunohistochemistry and quantification graph of the ratio of Olig2+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain (Scale bar=20 um; **p<0.05, ***p<0.01 vs. M0 conditioned media; n=5/group).
Fig. 3 Differentiation of SVZ-NSPCs in M2 conditioned media. M0, M1, or M2 conditioned media induced the differentiation of SVZ-NSPCs in the organotypic brain. (A and B) Immunohistochemistry and quantification graph of the ratio of DCX+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (C and D) Immunohistochemistry and quantification graph of the ratio of NeuN+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (E and F) Immunohistochemistry and quantification graph of the ratio of Olig2+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain (Scale bar=20 um; **p<0.05, ***p<0.01 vs. M0 conditioned media; n=5/group).CC BY-NC · PubMed Central
Fig. 4 TGF-α is one of the major cytokines in M2 conditioned media. (A) RT-PCR of IL-10 and TGF-α in M0, M1, or M2 conditioned media. IL-10 and TGF-α expression is significantly increased at the mRNA level in M2 conditioned media. (B) The graph depicts the relative mRNA expression of IL-10 and TGF-α in M0, M1, and M2 conditioned media. The expression of these genes is significantly increased in M2 conditioned media. (C) The expression level of TGF-α in M0, M1, and M2 conditioned media using ELISA assay. The quantity of TGF-α is significantly increased in M2 conditioned media compared with M1 (***p<0.01 vs. M0 conditioned media, n=5/group).
Fig. 4 TGF-α is one of the major cytokines in M2 conditioned media. (A) RT-PCR of IL-10 and TGF-α in M0, M1, or M2 conditioned media. IL-10 and TGF-α expression is significantly increased at the mRNA level in M2 conditioned media. (B) The graph depicts the relative mRNA expression of IL-10 and TGF-α in M0, M1, and M2 conditioned media. The expression of these genes is significantly increased in M2 conditioned media. (C) The expression level of TGF-α in M0, M1, and M2 conditioned media using ELISA assay. The quantity of TGF-α is significantly increased in M2 conditioned media compared with M1 (***p<0.01 vs. M0 conditioned media, n=5/group).CC BY-NC · PubMed Central
Fig. 5 Effect of TGF-α on the proliferation and neurogenesis of SVZ-NSPCs after cerebral ischemia. (A and B) Immunohistochemistry and quantification graph of the ratio of Ki67+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (C and D) Immunohistochemistry and quantification graph of the ratio of DCX+ and BrdU+ cells of SVZ-NSPCs in organotypic brain. (E and F) Immunohistochemistry and quantification graph of the ratio of NeuN+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (G and H) Immunohistochemistry and quantification graph of the ratio of Olig2+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain (Scale bar=20 um, **p<0.05 vs M0 conditioned media, n=5/group).
Fig. 5 Effect of TGF-α on the proliferation and neurogenesis of SVZ-NSPCs after cerebral ischemia. (A and B) Immunohistochemistry and quantification graph of the ratio of Ki67+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (C and D) Immunohistochemistry and quantification graph of the ratio of DCX+ and BrdU+ cells of SVZ-NSPCs in organotypic brain. (E and F) Immunohistochemistry and quantification graph of the ratio of NeuN+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain. (G and H) Immunohistochemistry and quantification graph of the ratio of Olig2+ and BrdU+ cells of SVZ-NSPCs in the organotypic brain (Scale bar=20 um, **p<0.05 vs M0 conditioned media, n=5/group).CC BY-NC · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 2

  1. Appel, 2011, Acta Myol, 30, 4
  2. Kornblum, 1997, J Comp Neurol, 380, 243, 10.1002/(SICI)1096-9861(19970407)380:2<243::AID-CNE7>3.0.CO;2-3 · DOI

Cited by

See all 65

Metadata

Authors
Choi, J. Y., Kim, J. Y., Kim, J. Y., Park, J., Lee, W. T., & Lee, J. E.
Affiliations
Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea
Venue
Experimental Neurobiology
Publisher
The Korean Society for Brain and Neural Science
Published
2017-02-28
Volume
26
Issue
1
Pages
33-41
ISSN
  • 1226-2560
  • 2093-8144
DOI
10.5607/en.2017.26.1.33
PMC
PMC5326713
Cited by
65
References
45
Language
en
Licence
creativecommons.org/licenses/by-nc/4.0 (tdm)
Funders
National Research Foundation of Korea (NRF-2016M3C7A1905098)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.