Effect Of Lipopolysaccharide-induced Immune Tolerance On Ischemic Stroke In Mice

Microglia,as resident immune cells of the central nervous system,plays an indispensable role in stroke.The latest research reports point out that microglia can be induced immune tolerance by LPS.However,there is little knowledge about the effects of lipopolysaccharide(LPS)induced microglia immune tolerance(LMT)on stroke and the change of metabolic state in this process.In this experiment,we first injected 0.5 mg/kg of LPS into mice by intraperitoneal injection for 4 consecutive days to construct an LPS-induced immune tolerance model.Then acute ischaemic stroke model was established by Rose bengal photothrombosis after four days in LMT.Nissl and Fluoro-Jade C staining were used to detect the changes of infarct volume and degenerative neurons.Microglia activation and the expression of inflammation cytokines were detected by immunostaining of Iba-1,i NOS and ARG-1.Cultured BV2 cells was used to investigate the change of physiological status in migration,phagocytosis,inflammatory and proliferation while they were treated with LPS after oxygen–glucose deprivation.2-Deoxy-D-arabinose-hexose(2-DG)and Interferon-gamma(IFN-γ)were used to evaluate the change of metabolic status.The results showed that LPS-induced immune tolerance decreased the infarct volume,inhibit activation of microglia and pro-inflammatory response but enhanced the anti-inflammatory response in mice after stroke.The results showed that LPSinduced immune tolerance reduced migration,the expression of pro-inflammatory cytokines and proliferation of BV2 cells,but enhanced phagocytosis in BV2 cells after OGD treatment.The above results indicated that the LPS induced immune tolerance reduced the ischemic stroke damage,which may be closely related to the changes in the immune function of microglia.Inhibiting glycolysis or enhancing oxidative phosphorylation broke the immune tolerance status in microglia cells.These results provided new insights to the investigation in the relationship between the metabolic state and immune status in microglia.Meanwhile these results provided new ideas for the treatment of ischemic stroke.