Interaction of Microglia and Astrocytes in the Neurovascular Unit

Abstract

The interaction between microglia and astrocytes significantly influences neuroinflammation. Microglia/astrocytes, part of the neurovascular unit (NVU), are activated by various brain insults. The local extracellular and intracellular signals determine their characteristics and switch of phenotypes. Microglia and astrocytes are activated into two polarization states: the pro-inflammatory phenotype (M1 and A1) and the anti-inflammatory phenotype (M2 and A2). During neuroinflammation, induced by stroke or lipopolysaccharides, microglia are more sensitive to pathogens, or damage; they are thus initially activated into the M1 phenotype and produce common inflammatory signals such as IL-1 and TNF-α to trigger reactive astrocytes into the A1 phenotype. These inflammatory signals can be amplified not only by the self-feedback loop of microglial activation but also by the unique anatomy structure of astrocytes. As the pathology further progresses, resulting in local environmental changes, M1-like microglia switch to the M2 phenotype, and M2 crosstalk with A2. While astrocytes communicate simultaneously with neurons and blood vessels to maintain the function of neurons and the blood-brain barrier (BBB), their subtle changes may be identified and responded by astrocytes, and possibly transferred to microglia. Although both microglia and astrocytes have different functional characteristics, they can achieve immune "optimization" through their mutual communication and cooperation in the NVU and build a cascaded immune network of amplification.

Neuroinflammation in Ischemic Stroke: Focus on MicroRNA-mediated Polarization of Microglia

“…Microglia play a key role following stroke, and the M1 phenotype typically releases pro-inflammatory mediators, while the M2 phenotype suppresses the harmful processes associated with ischemia. Numerous studies have shown that the interaction of various cells (i.e., astrocytes, oligodendrocytes, neurons), specific cytokines, drugs, and other extracellular components can promote microglia phenotype conversion (Kim and Cho, 2016 ; Pepe et al, 2017 ; Zhang et al, 2019a ; Liu L. R. et al, 2020 ). Furthermore, a large number of studies have focused on the combined intervention of miRNAs and microglia; however, the role of miRNAs in the phenotypic transformation of microglia might not be limited to reducing the release of pro-inflammatory factors (Kim and Cho, 2016 ).…”

The NFκB Antagonist CDGSH Iron-Sulfur Domain 2 Is a Promising Target for the Treatment of Neurodegenerative Diseases

“…Based on this immunocompetent response, aggregation of pattern recognition receptors (PRRs), which are mainly toll-like receptors (TLRs), activate microglia and consequently trigger neuroinflammation [ 18 ]. Stimulated M1 phase microglia have been indicated to activate astrocytes directly [ 19 ]. Glia-mediated neuroinflammation has been linked to the pathogenesis of various NDs, including AD, PD, and MS [ 20 , 21 ].…”

Astrocyte-secreted chordin-like 1 regulates spine density after ischemic stroke

“…The immune response in ischemic stroke is regulated by various glial cell types that also interact among themselves to regulate inflammation, and these glia-mediated mechanisms can exert both beneficial and detrimental effects (13). Astrocytes and microglia are two important components of the neurovascular unit, and both are activated in response to ischemic stroke, as well as other types of CNS injuries (38). It has been previously shown that activated microglia can induce reactive astrogliosis with neurotoxic effects (39), but the mechanisms that regulate microglia activation are still not completely clear.…”