Effect of metformin on cognitive function in mice with cerebral ischemia/reperfusion injury and its mechanism
Objective To evaluate the effect of metformin on cognitive function in cerebral ischemia/reperfusion(I/R)mice and its mechanism.Methods Forty male C57BL/6 mice,weighing(23±2)g,7-8 weeks old,were randomly divided into four groups:sham group,I/R group,I/R+100 mg/kg metformin group(low-dose group)and I/R+200 mg/kg metformin group(high-dose group),with 10 mice in each group.The mice in sham group underwent the same surgical procedures except for the absence of the insertion of the filament.In I/R group,the mice were subjected to middle cerebral artery occlusion(MCAO)for 60 min and then reperfu-sion for 7 d.Mice in low-dose group and high-dose group were intragastrically perfused with 100,200 mg/kg metformin solution every day for 7 d after I/R.The learning and memory-related indicators of mice in each group were evaluated using the Morris water maze,the brain edema of mice in each group was assessed using the dry-wet weight method,the morphological changes of neurons in mice in each group were evaluated using HE staining,the content of brain-derived neurotrophic factor(BDNF)and the activity of superoxide dismutase(SOD)in brain tissues of mice in each group were detected using ELISA kits.Results Compared with sham group,the spontaneous alternation accuracy,the target quadrant time and the number of crossing platforms were decreased in I/R group(P＜0.05),the escape latency was increased(P＜0.05),the water content of brain tissue was increased(P＜0.05),BDNF content and SOD activity were decreased(P＜0.05),and the neuronal degeneration were increased in I/R group.Compared with I/R group,the target quadrant time was increased in low-dose group(P＜0.05).Compared with I/R group,the spontaneous alternation accuracy,the target quadrant time and the number of crossing platforms were increased in high-dose group(P＜0.05),the escape latency was decreased(P＜0.05),the water content of brain tissue was decreased(P＜0.05),BDNF content and SOD activity were increased(P＜0.05),and the neuronal degeneration were decreased in high-dose group.Conclusion Metformin(200 mg/kg)post-treatment could improve the cognitive function of cerebral ischemic mice,which may be related to the reduction of brain edema,the improvement of neuronal degeneration,and the increase of BDNF content and SOD activity in the brain.
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