Function Of M1 And M2 Microglia/Macrophages After Ischemic Stroke In Mice

Ischemic stroke is one of the most common cerebrovascular diseases,which seriously affects the national health with its high incidence and high lethality,and there is still no effective treatment for the cerebral ischemic lesion.When the brain is damaged by ischemia,microglia/macrophages(MG/MP)can rapidly activate and polarize into two different phenotypic subtypes,M1 and M2 subtypes,which are widely identified by their distinct cell surface receptors and play important roles in ischemia progression.However,the specific functions of M1 and M2 MG/MP in ischemic brain injury have been poorly understood.In this study,we established a focal ischemia pathological model in mice,and examined the polarization dynamic patterns of M1 and M2 MG/MP during the subacute stage of ischemia.Our results indicated that the density of M1 cells were maximized at 3 days after focal ischemia.Subsequently,the density of M2 cells increased and reached maximum density at 5 days after ischemia.Results of qRT-PCR indicated that the expression level of M1 phenotype specific genes on the third day after ischemia was higher than that on the seventh day,but specific genes(Cd206/ Tgf-β)of M2 cells underwent gradually up-regulation till the seventh day after the induction of ischemia.Then we used drugs to selectively eliminate M1 or M2 MG/MP.Results showed that with the selective elimination of M1 cells,pro-inflammatory genes were significantly down-regulated while the expression level of anti-inflammatory genes and vascular endothelial associated genes showed no significant difference compared to those of Control group.At the meantime,the infarct volume and the density of FJC/+ cells was decreased compared to those in the mice of Control group.Additionally,results of behavioral test showed improved behavioral performance of mice.On the other hand,selective elimination of M2 cells resulted in significant down-regulation of antiinflammatory genes and vascular endothelial associated genes,but the expression level of pro-inflammatory genes showed significant up-regulation compared to those of Control group.Meanwhile,the infarct volume and density of FJC/+ cells were significantly increased,and the behavioral performance of mice decreased.Our study proved that activated MG/MP mainly polarized to M1 subtype that had facilitated neuroinflammation and had negative impact on the brain during early subacute stage of cerebral ischemia.Subsequently,MG/MP intended to polarize to M2 subtype which reduced the neuroinflammatory response and had positive effect on neuro-repair.Our research has provided theoretical foundation for regulating M1 or M2 MG/MP activation/polarization,and also offered reference to the early clinical treatment of acute ischemic stroke.