The Effect Of FTY720-mediated Microglia Polarization In Ischemic White Matter Injury

Objective:To investigate the effect of S1 P receptor agonist FTY720 on myelination and cognitive dysfunction in mice in the mouse cerebral hypoperfusion model,and the effect of FTY720 on microglia activation,microglia polarization,and the effect of FTY720 on oligodendrocyte survival,oligodendrocyte proliferation and oligodendrocyte differentiation.Methods:The bilateral common carotid artery stenosis(BCAS)model was established.8-arm maize test was used to examine reference memory faults and the working memory loss,both of which are designed for the effect of FTY720 on cognitive function.LFB staining was used to observe the integrity of myelin sheath structure in BCAS mice.Immunofluorescence staining was used to observe the effect of FTY720 on oligodendrocytes,microglia,myelin,and axon in BCAS mice at different time points(3rd,10 th day,and 1st month).Isolated microglia from neural cell suspensions using magnetic beads conjugated to CD11 b monoclonal antibody to obtain the entire myeloid population.Polarization states of CD11b+microglia were evaluated by expression of M1 surface marker CD16/32 、 CD86 and M2 surface marker CD206、CD23.RT-PCR was used to examine the polarization of microglia in vitro.ELISA was used to detect the supernatant of microglial cells in order to measure the levels of TNF-α,TGF-β,IL-1βand IL-13.The supernatant of microglial cells was added to the purified oligodendrocyte precursor cells,then the differentiation of oligodendrocyte precursor cells were detected by immunofluorescence staining.Results:LFB staining certificated that FTY720 can reduce the damage in white matter from BCAS.FTY720 inhibits the activation of microglia,promotes the microglia toward M2 polarization,promotes survival and proliferation and differentiation of oligodendrocyte,reduces the cognitive impairment in white matter from BCAS.FTY720 promotes the microglia toward M2 polarization and promotes oligodendrocyte differentiation in vitro.Conclusion:FTY720 modulates microglia toward M2 polarization in the mouse cerebral hypoperfusion model and promotes the survival,proliferation and differentiation of oligodendrocytes,reduces myelination,improves ischemic white matter damage,and reduces the cognition impairment.