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Updated: Oct 8, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Metformin-dependent variation of microglia phenotype dictates pericytes maturation under oxygen-glucose deprivation
Mohammad Hossein Geranmayeh1,2, Reza Rahbarghazi3,4, Nazli Saeedi1
1Research Center for Pharmaceutical Nanotechnology (RCPN), Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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). Incubation of pericytes with microglia-conditioned media pretreated with metformin under glucose- and oxygen-free conditions or normal conditions increased pericyte maturity. These changes coincided with the reduction of the Sox2/NG2 ratio compared to the control pericytes (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.
Insights
Metformin helps balance microglial phenotypes during brain injury. This influences pericyte maturation, crucial for blood-brain barrier function and brain homeostasis.
Area of Science:
- Neuroscience
- Cell Biology
- Vascular Biology
Background:
- Blood-brain barrier resident cells, including microglia and pericytes, are vital for brain homeostasis and function.
- Microglia can adopt different phenotypes (M1/M2) in response to pathological conditions.
- Pericyte maturity influences blood-brain barrier integrity.
Purpose of the Study:
- To investigate the effect of metformin on microglial M1/M2 phenotype balance under oxygen-glucose deprivation (OGD).
- To explore how microglial phenotype modulation impacts pericyte maturation.
- To understand the interplay between microglia and pericytes in the context of ischemic and hypoxic conditions.
Main Methods:
- Isolation of rat brain microglia and pericytes.
- Treatment of microglia with metformin under OGD conditions.
- Incubation of pericytes with microglia-conditioned media.
- Analysis of microglial phenotype (CD206+) and pericyte maturity markers (Sox2/NG2 ratio).
Main Results:
- Metformin suppressed the shift of microglia towards the M2 phenotype under OGD conditions (p < .01).
- Pericyte maturity increased when incubated with metformin-pretreated microglia-conditioned media.
- This increase in pericyte maturity correlated with a reduced Sox2/NG2 ratio (p < .05).
Conclusions:
- Metformin modulates microglial phenotype balance, reducing M2 polarization under ischemic conditions.
- Microglial phenotype plays a significant role in regulating pericyte maturation.
- A close interplay exists between microglia and pericytes, impacting blood-brain barrier function during ischemia and hypoxia.
