RT - Journal Article T1 - A comprehensive approach to investigate the contradictory effects of metformin therapy in cerebral ischemic injury JF - Physiol-Pharmacol YR - 2015 JO - Physiol-Pharmacol VO - 19 IS - 3 UR - http://ppj.phypha.ir/article-1-1124-en.html SP - 146 EP - 157 K1 - Metformin K1 - AMPK K1 - Glucose K1 - Brain K1 - Ischemia AB - Ischemic brain injury involves a complex sequence of excitetoxic and oxidative events. Metformin is proposed as one of the potential candidates for returning the body to its basic homeostasis in ischemic situations. Metformin can either protect or damage cells by activating AMP-activated protein kinase (AMPK) and its downstream factors so, it has a dual role in the cerebral ischemia context, but more investigations are needed to define its exact underlying mechanism. Herein, we classify the controversial results of metformin therapy in the experimental models of brain ischemia central and peripheral injection of metformin, chronic and acute treatment, pre- and post-treatment with metformin, tissue-specific role of metformin, dose-specific effect of metformin, age-dependent aspects of metformin therapy. Categorizing different types of cerebral ischemia is important in investigating the dual role of metformin. Due to the variations in metformin therapy, it can be used for chronic treatment, but the patients must be informed about its harmful effects. Although the mechanisms in which AMPK protects/degenerates neurons against ischemic stress situation are still unknown. LA eng UL http://ppj.phypha.ir/article-1-1124-en.html M3 ER -