leads to increased spread of inflammation and serum proteins, increased loss of neural tissue, and decreased functional recovery in rodents [11, 12, 32, 45]. New astrocyte borders and reorganized tissue architecture are essentially permanent [32]. Newly proliferated astrocytes can derive from different progenitor sources, including proliferation of local astrocytes [13, 46–48] and periventricular neural progenitors [45]. At present, it appears that proliferation of reactive astrocytes is associated primarily with border formation and that most border forming astrocytes around CNS lesions are newly proliferated [13, 32]. Nevertheless, the degree to which reactive astrocyte proliferation may or may not occur in other contexts is not clear and is not well-studied. Because astrocytes divide rarely in healthy tissue [13], proliferation is an important means of discriminating different subtypes of reactive astrocytes, those that proliferate, and those that do not.Non-proliferative reactive astrocytes maintain their locations and fundamental features of cell structure, cellular interactions and functions in neural tissue that is not overtly damaged and retains its tissue architecture, but nonetheless responds to injury or disease (Key Figure, Figure 2D) [1, 8, 49]. Depending on the nature and severity of the insult, non-proliferative reactive astrocytes exhibit variable changes in molecular expression [30, 50] and variable
