Reactive astrocytes also have the potential to contribute to maladaptive effects in various ways through loss- or gain-of-functions that occur in response to non-cell-autonomous reactivity-driving signals. As described above, in healthy CNS tissue, astrocytes exert many essential functions that are crucial for neural circuit function, neurological function and behavior [7]. The degree to which essential astrocyte functions might be attenuated or lost by reactive astrocytes and thereby cause detrimental effects in different disorder contexts is poorly understood and represents yet another important goal for future study. In this regard, a reduced proliferative response of reactive astrocytes in the aged brain can contribute to age-related vulnerability to traumatic injury in mice [78], and this is interesting as it might also contribute to increased vulnerability to aging-related neurodegenerative conditions [29]. As a counterpoint to the loss of beneficial astrocyte functions, there is a potential for reactive astrocytes to exert detrimental or maladaptive effects through inappropriate gain-of-functions, which might be driven by chronic exposure to reactivity triggers (Key Figure, Figure 2F,G). For example, transgenically-targeted molecular deletion studies show that attenuation of pro-inflammatory signaling
