Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats

Mojtaba Karimipour, Sara Shojaei Zarghani, Majid Mohajer Milani, Hamid Soraya


Objective: To explore the effects of pre versus post ischemic treatment with metformin after global cerebral ischemia in rats.

Methods: Male Wister rats underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Metformin (200 mg/kg) or vehicle was given orally by gavage for 7-14 days. Rats were divided into: control, metformin pre-treatment, metformin post-treatment and metformin pre and post continuous treatment groups. Cerebral infarct size, histopathology, myeloperoxidase and serum malondialdehyde were measured 7 days after ischemia.

Results: Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level. Metformin pre-treatment and metformin post-treatment reduced infarct size compared with the control group, but it was not significant in the pre and post continuous treatment group.

Conclusion: Our findings suggest that pre-treatment with metformin in comparison with post-treatment in experimental stroke can reduce the extent of brain damage and is more neuroprotective at least in part by inhibiting oxidative stress and inflammation.


Global cerebral ischemia; Metformin; Oxidative stress; Inflammation

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