Metabolic reprogramming and astrocytes polarization following ischemic stroke

Astrocytes are critical for maintaining neuronal activity. Activation of astrocytes, occurs within minutes from ischemic stroke onset due to ischemic causes and subsequent inflammatory damage. Activated astrocytes, also known as reactive astrocytes, are divided into two different phenotypes: A1 (pro-inflammatory) and A2 (anti-inflammatory) astrocytes. A2 astrocytes support neuronal survival and promote tissue healing, while A1 astrocytes have neurotoxic effects. Thus, polarization of reactive astrocyte into A1 or A2 genotype is closely correlated with the development of cerebral ischemia/reperfusion (I/R) injury. Metabolic reprogramming is a process that various metabolic pathways upregulate in cells to balance energy, alter their phenotype, and produce building-block requirements. A1 and A2 astrocytes display different metabolic reprogramming, such as glycolysis, glutamate uptake, and glycogenolysis. Accumulating evidence suggested that manipulation of energy metabolism homeostasis can induce astrocytes to switch from A1 to A2 phenotype. This review disucss the potential factors in affecting astrocytic polarization, emphasizes metabolic reprogramming in reactive astrocytes within the pathophysiological context of cerebral I/R, and explores the relationship between metabolic reprogramming and astrocytic polarization. Importantly, we reveal that regulating metabolic reprogramming in reactive astrocytes may be a potential therapeutic target for cerebral I/R injury.