from multiple laboratories showing that transgenically attenuating astrocyte reactivity via selective deletion of a wide variety of different types of molecules, including membrane receptors, transcriptional regulators, or effector molecules, can exacerbate tissue injury and worsen functional outcome in models of essentially all forms of CNS disorders, including infection [19], traumatic injury [65], autoimmune attack [14, 15, 70]; stroke [45, 71]; and multiple degenerative disease models [28, 72–75] as reviewed in detail elsewhere [31, 32]. Moreover, recent evidence suggests that reactive astrocytes can contribute to synapse remodeling and circuit reorganization [6, 33, 37], and even the longstanding view that reactive astrocytes are the primary cause for the failure CNS axon regeneration has been overturned [57, 69, 76, 77]. Together, these findings support the concept that in multiple disorder contexts, normal reactive astrocytes can contribute adaptive functions that help preserve neural tissue and maintain neurological functions. Nevertheless, how reactive astrocytes implement the broad adaptive effects that are revealed by loss-of-function experiments is poorly defined; therefore, dissecting the cellular and molecular mechanisms that mediate reactive astrocyte effects in specific disorder contexts represents a key goal for future study.
