A1/A2 astrocytes in central nervous system injuries and diseases: Angels or devils?

Astrocytes play a pivotal role in maintaining the central nervous system (CNS) homeostasis and function. In response to CNS injuries and diseases, reactive astrocytes are triggered. By purifying and genetically profiling reactive astrocytes, it has been now found that astrocytes can be activated into two polarization states: the neurotoxic or pro-inflammatory phenotype (A1) and the neuroprotective or anti-inflammatory phenotype (A2). Although the simple dichotomy of the A1/A2 phenotypes does not reflect the wide range of astrocytic phenotypes, it facilitates our understanding of the reactive state of astrocytes in various CNS disorders. This article reviews the recent evidences regarding A1/A2 astrocytes, including (a) the specific markers and morphological characteristics, (b) the effects of A1/A2 astrocytes on the neurovascular unit, and (c) the molecular mechanisms involved in the phenotypic switch of astrocytes. Although many questions remain, a deeper understanding of different phenotypic astrocytes will eventually help us to explore effective strategies for neurological disorders by targeting astrocytes.