Metformin-dependent variation of microglia phenotype dictates pericytes maturation under oxygen-glucose deprivation

Abstract

Blood-brain barrier resident cells are in the frontline of vascular diseases. To maintain brain tissue homeostasis, a series of cells are integrated regularly to form the neurovascular unit. It is thought that microglia can switch between M1/M2 phenotypes after the initiation of different pathologies. The existence of transition between maturity and stemness features in pericytes could maintain blood-brain barrier functionality against different pathologies. In the current study, the effect of metformin on the balance of the M1/M2 microglial phenotype under oxygen-glucose deprivation conditions and the impact of microglial phenotype changes on pericyte maturation have been explored. Both microglia and pericytes were isolated from the rat brain. Data showed that microglia treatment with metformin under glucose- and oxygen-free conditions suppressed microglia shifting into the M2 phenotype (CD206+ cells) compared to the control (p < .01) and metformin-treated groups (p < .05). Data revealed the close microglial-pericytic interplay under the ischemic and hypoxic conditions and the importance of microglial phenotype acquisition on pericyte maturation.