Objective To explore the protective effects and the underlying mechanisms of bone marrow mesenchymal stem cells(BMSCs)on the brain in microgravity environment.Methods The physiological effects of microgravity were simulated with the hindlimb unloading(HU)mouse model.The animals were divided into 3 groups:the control group(wild-type mice),the hindlimb unloading(HU)group,and the BMSCs treatment group,with six in each.RT-qPCR was adopted to determine the expression levels of pro-inflammatory cytokines(Il-6,Il-1β and Tnf-α)in the cerebral cortex;immunohistochemistry was performed to evaluate the proportions of microglia(IBA-positive)and astrocytes(GFAP-positive);Western blot was used to measure the expression levels of apoptosis-and senescence-related molecules(BAX,BCL-2,p21,and p53).Results Compared with wild-type mice,the expression levels of Il-6,Il-1β and Tnf-α in the cerebral cortex of HU mice were significantly increased(P＜0.05),the expression level of BAX,p21 and p53 was also significantly increased(P＜0.05).However,the expression level of BCL-2 protein were significantly decreased(P＜0.05).The proportion of micro-glia(IBA1 positive)and astrocytes(GFAP positive)was increased(P＜0.05);After BMSCs treatment,the expression level of Il-1β in the cerebral cortex of HU mice was significantly decreased(P＜0.05),the expression levels of BAX,p21 and p53 were significantly decreased(P＜0.05),and the expression level of BCL-2 protein was significantly increased(P＜0.05).The proportion of microglia(IBA1 positive)and astrocytes(GFAP posi-tive)decreased(P＜0.05).Conclusions BMSCs potentially relieve the detrimental effects of simulated micro-gravity on mouse brain by inhibiting inflammation,apoptosis and cellular senescence.