Figure 1.

Under the stimulation of injury and disease, (A) naive astrocytes are activated into functionally heterogeneous reactive astrocytes (RAs); this heterogeneity is determined by the background of the astrocytes. The Plaur, Mmp2, Mmp13, Axin2, Nes, and Ctnnb1 genes are markers of RAs. In an inflammatory background, (B) A1 astrocytes are proposed to be a subpopulation of neurotoxic RAs and are marked by C3 expression. (C) A2 astrocytes are induced by ischemia and hypoxia and are indicated to play a neuroprotective role in injury and disease. A2 astrocytes can be distinguished by the expression of S100A10. C3⁺ A1 astrocytes have long dendrites, while S100a10⁺ A2 astrocytes have hypertrophic cell bodies with few dendrites. There are other as yet unidentified subpopulations of RAs that also play an important role in disease, such as (D) and (E). As the disease progresses, there is an overlap of RA subpopulations and chondroitin sulfate proteoglycan (CSPG) deposits, which together induce the conversion of RAs to SAs (F). Cdh2, Sox9, and CSPG-related genes (Csgalnact1, Chst11, Pcan, Acan, and Slit2) are markers of scar-forming astrocytes (SAs).