basic cell structure, tissue architecture, and functional interactions they exhibited in healthy tissue (Key Figure, Figure 2D). Basic features of these two broad subtypes can be summarized as follows: Proliferative, border-forming reactive astrocytes surround damaged tissue that contains leukocyte infiltration, stromal-cell proliferation and fibrosis after trauma, ischemia, infection, autoimmune inflammation, toxin accumulation, blood-brain barrier (BBB) leak or neurodegenerative disease (Key Figure, Figure 2C) [1, 8, 11, 29, 32]. These new astrocyte borders separate and isolate damaged, inflamed and fibrotic tissue from adjacent viable neural tissue in a manner analogous to astrocyte limitans borders that separate neural from non-neural tissue along the meninges in healthy CNS [32]. Loss-of-function studies from multiple laboratories show that border-forming reactive astrocytes interact with non-neural stromal and immune cells, which they attract, instruct and corral (reviewed elsewhere [13, 32]). Border-forming astrocytes are essential for reforming the BBB around lesions and for protecting and preserving adjacent functional neural tissue, such that loss or attenuation of these cells 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
