Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an an...Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an anti-inflammatory M2 phenotype in the early stage of ischemia,they transform progressively into a proinflammatory M1 phenotype.Bone marrow-derived mesenchymal stem cells(BMSCs)may be used to treat ischemic injury through regulating the poststroke inflammatory response.However,the mechanism by which BMSCs can treat ischemic stroke remains unclarified.Objective:This study aimed to investigate whether BMSCs shift M1-to-M2 phenotype transformation of mi-croglia/macrophages and enhance neurogenesis in a rat transient middle cerebral artery occlusion(tMCAO)model.Methods:Ninety-minute tMCAO was applied to the rats,followed by reperfusion.BMSCs were transplanted into the rats via intravenous injection at 24 h after tMCAO.After being randomly divided into the sham group,the MCAO group,and the BMSCs group,the rats’behavior was assessed at 1,3,7,and 14 days following tM-CAO.qRT-PCR,double-immunofluorescence staining,and Western blot were performed at 3 and 14 days after tMCAO to determine M1/M2 polarization of microglia/macrophages.Neurogenesis was examined by double-immunofluorescence staining at 14 days after tMCAO.Expression of brain-derived neurotrophic factor(BDNF)was measured on the protein level by immunofluorescence staining at 3 and 14 days after tMCAO.Results:We found that BMSCs treatment promoted the recovery of neurological function after tMCAO,inhibited the expression of TNF𝛼,iNOS and CD16/32,which are markers of M1 microglia/macrophage,and enhanced the expression of IL10,TGF𝛽and CD206 that are markers of M2 microglia/macrophage.Moreover,BMSCs treatment promoted neurogenesis and M2-derived BDNF expression after tMCAO.Conclusion:It is indicated by the results that BMSCs modulate neuroinflammation and enhance neurogenesis,which could be due to transforming microglia/macrophages from the M1 polarization state towards M2 in a rat tMCAO model.展开更多
基金supported by the National Natural Sci-ence Foundation of China(Grant Nos.81274113,81873028,81903949)the Natural Science Foundation of Zhejiang Province(Grant No.LQ19H290004).
文摘Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an anti-inflammatory M2 phenotype in the early stage of ischemia,they transform progressively into a proinflammatory M1 phenotype.Bone marrow-derived mesenchymal stem cells(BMSCs)may be used to treat ischemic injury through regulating the poststroke inflammatory response.However,the mechanism by which BMSCs can treat ischemic stroke remains unclarified.Objective:This study aimed to investigate whether BMSCs shift M1-to-M2 phenotype transformation of mi-croglia/macrophages and enhance neurogenesis in a rat transient middle cerebral artery occlusion(tMCAO)model.Methods:Ninety-minute tMCAO was applied to the rats,followed by reperfusion.BMSCs were transplanted into the rats via intravenous injection at 24 h after tMCAO.After being randomly divided into the sham group,the MCAO group,and the BMSCs group,the rats’behavior was assessed at 1,3,7,and 14 days following tM-CAO.qRT-PCR,double-immunofluorescence staining,and Western blot were performed at 3 and 14 days after tMCAO to determine M1/M2 polarization of microglia/macrophages.Neurogenesis was examined by double-immunofluorescence staining at 14 days after tMCAO.Expression of brain-derived neurotrophic factor(BDNF)was measured on the protein level by immunofluorescence staining at 3 and 14 days after tMCAO.Results:We found that BMSCs treatment promoted the recovery of neurological function after tMCAO,inhibited the expression of TNF𝛼,iNOS and CD16/32,which are markers of M1 microglia/macrophage,and enhanced the expression of IL10,TGF𝛽and CD206 that are markers of M2 microglia/macrophage.Moreover,BMSCs treatment promoted neurogenesis and M2-derived BDNF expression after tMCAO.Conclusion:It is indicated by the results that BMSCs modulate neuroinflammation and enhance neurogenesis,which could be due to transforming microglia/macrophages from the M1 polarization state towards M2 in a rat tMCAO model.
