Reactive astrocytes are essential components of multicellular CNS innate immunity that respond to all forms of CNS injury and disease. There is mounting interest in strategies to manipulate astrocyte reactivity in CNS disorders (Box 2). Doing so will require a detailed understanding of what astrocyte reactivity is, what it does and how it is regulated under varying conditions (see outstanding questions). Accumulating evidence argues that astrocyte reactivity cannot be parsed into a few broad and stereotypic programs that are either beneficial or detrimental to the host. Instead, multiple findings point towards reactive astrocytes as being able to adopt a broad spectrum of nuanced changes that are disorder and context specific. There is a growing need to develop a detailed understanding of how specific astrocyte functions change during different disorders and how this may vary in different tissue regions. This knowledge is required to be able to develop evidence-based therapeutic approaches that might beneficially modulate astrocyte reactivity in a disorder- and context-specific manner.
