Objective lo investigate the effect of intracerebroventricular injection of lipopolysaccharide(LPS)on hippocam-pal-dependent spatial memory in mice.Methods A total of 14 wild-type mice,aged 3 months,were randomly divided into con-trol group with 6 mice and LPS group with 8 mice,and the mice in the control group were given intracerebroventricular injection of 3 μL normal saline,while those in the LPS group were given intracerebroventricular injection of 1 g/L LPS.The water maze test was used to observe the spatial memory ability of mice.A total of 10 wild-type mice,aged 3 months,were selected for water maze training and were randomly divided into control group and LPS group after spatial memory formation on day 7,with 5 mice in each group.The mice in the control group were given intracerebroventricular injection of 3 μL normal saline,while those in the LPS group were given were given intracerebroventricular injection of 1 g/L LPS,and training and testing were performed on day 9.Mouse BV2 microglial cells were stimulated with 1 mg/L LPS to measure the changes in the inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results The water maze test showed that during the training phase for spatial memory acquisition,there was no significant difference in the time spent to find the target platform between the LPS group and the control group,with no significant interaction effect between training time and drug type(F interaction=0.712,P=0.616 8);during the test phase for spatial memory formation,the LPS group showed no significant difference in the proportion of exploration time between the target quadrant and the other quadrants(P>0.05);however,after memory formation,intracerebroventricular injec-tion of LPS resulted in impaired retrieval of spatial memory in mice(P<0.05).BV2 cells in the LPS group showed significant in-creases in the mRNA expression levels of TNF-α and IL-6 at different treatment times(P<0.05).Conclusion Hippocampal inflammation induced by LPS can lead to deficits in both acquisition and retrieval of spatial memory in mice,which may be associa-ted with the activation of microglial cells.