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

 Ja Yong Choi  ;  Jong Youl Kim  ;  Jae Young Kim  ;  Joohyun Park  ;  Won Taek Lee  ;  Jong Eun Lee 
 EXPERIMENTAL NEUROBIOLOGY, Vol.26(1) : 33-41, 2017 
Journal Title
Issue Date
Ischemic stroke ; TGF-α ; microglia ; neural stem/progenitor cells ; neuronal differentiation ; proliferation
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 phenotype-conditioned 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.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Jong Youl(김종열) ORCID logo https://orcid.org/0000-0002-8340-2894
Park, Joohyun(박주현) ORCID logo https://orcid.org/0000-0002-0897-4665
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
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