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 degrees of cellular hypertrophy [1]. Notably, the discrete, non-overlapping cellular domains exhibited by astrocytes in healthy grey matter are preserved such that hypertrophy occurs primarily within these individual cellular domains [51]. Thus, non-proliferative reactive astrocytes are likely to continue functionally interacting with the same cellular elements that they interact with in healthy tissue, including for example, neurons, synapses and blood vessels. In support of this notion, reactive astrocytes in rodents are reported to promote synapse recovery after axonal injury via Stat3-dependent mechanisms ((GFAP)-Cre/Stat3-loxP conditional knockout mice) [52]; moreover, loss of functions via atypical reactive astrocytes has been associated with seizure genesis following repetitive mild head trauma [53]; also, low glutathione concentrations -- which can occur in stroke -- can dysregulate astrocyte-mediated vasodilation [54]. Nevertheless, in spite of these few early studies, surprisingly little is currently known about how different forms of non-proliferative astrocyte reactivity alter essential astrocyte functions. As discussed above, in healthy CNS, astrocytes interact with many cell types
