Large scale molecular screening studies are revealing different molecular expression profiles of reactive astrocytes in different disorders based either on bulk analyses of whole tissue samples, or on single cell analyses [17, 23, 34, 50, 55–61, 63]. Such observations raise questions about whether there are consistent patterns of molecular expression that might serve as ‘signatures’ for particular astrocyte functional subtypes or states and what type of nomenclature might be appropriately applied. For example, in some single-cell molecular analyses, astrocyte clusters most prevalent in baseline healthy tissue are referred to as ‘homeostatic’, and astrocytes in diseased tissue that are most different from ‘homeostatic’ astrocytes, are referred to as ‘disease-associated’ [63]. Caution is urged with regards to this practice. First, astrocytes in healthy CNS exhibit multiple different molecular expression patterns that are associated with homeostatic functions [36]. Second, assigning the term ‘homeostatic’ only to astrocytes in healthy tissue implies that reactive astrocytes are by definition ‘nonhomeostatic’, which can be misleading because disease-associated changes undergone by certain reactive astrocytes can exert homeostatic activities that preserve BBB function [64], tissue integrity [32], and neurological
