Metformin reduces neuronal damage and promotes neuroblast proliferation and differentiation in a cerebral ischemia/reperfusion rat model

Abstract

According to the previous research, metformin, a medication utilized for type 2 diabetes management, inhibits neural aging and reduces infarct size by enhancing angiogenesis in a mouse stroke model. What is more, metformin administration also promotes neural precursor cells proliferation, migration, as well as differentiation for newborn mice with hypoxia–ischemia brain injury. However, whether metformin regulates neurogenesis in an adult rat ischemia/reperfusion (I/R) model remains unclear. The current research found that metformin administration reduced neuronal damage in the CA1 area of hippocampus in a rat model of I/R. The number of neuronal nuclei positive neuron was significantly increased and glial fibrillary acidic protein positive astrocyte became obviously declined in the CA1 region in I/R rats treated with metformin. It was further demonstrated that metformin promoted neuroblasts proliferation and neuronal differentiation in the subgranular zone of the dentate gyrus and inhibited the formation of astrocyte. Our study indicates that activation of endogenous neuroblasts using metformin will become a favorable target in therapeutic intervention of cerebral ischemia injury models.