Pretreatment effects of metformin on behavioral manifestations of global ischemia/reperfusion injury in rats

Introduction: Metformin (MET) as an oral antidiabetic drug has pleiotropic effects such as antioxidative and neuroprotective properties. In the current study we aimed to investigate the probable effects of Pretreatment MET therapy in global ischemia-reperfusion in rats. Materials and Methods: In this study, 40 male Wistar rats (200-220 g) were used. Animals were randomly divided into four groups of ten: sham group, ischemic group, ischemic + metformin group and metformin group. MET was administered orally at doses of 100 for 14 days then the rats underwent global ischemia-reperfusion and the treatment continued for 7 days. Depressive-like behavior was assessed by forced swimming test. Cognitive function was evaluated by Y-maze continuous alternation task and Morris water maze. The brains were assessed for the activity of superoxide dismutase (SOD) as well as level of brain-derived neurotrophic factor (BDNF). Results: global ischemia-reperfusion caused depression and declined the cognitive function (p<0.001( as well as BDNF (p<0.001( level and SOD (p<0.01 (activity. Pretreatment with MET reduced the depressive-like behavior (p<0.05( and attenuated the cognitive impairments (p<0.01( in ischemic rats. Moreover, MET increased the BDNF (p<0.001( level in the brains of ischemic animals Conclusion: Our results recommended that chronic pretreatment MET therapy could improve behavioral disorders following global ischemia-reperfusion and could be used as a novel therapeutic approach for the treatment of brain ischemic conditions.