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In the injured central nervous system (CNS), reactive astrocytes form a glial scar and they are considered a physical barrier to prevent axonal regeneration by producing axonal growth inhibitors, such as chondroitin sulfate proteoglycans. However, the physiological role of reactive astrocytes remains to be elucidated. In this review, we showed that reactive astrocytes play a crucial role in wound healing and functional recovery. At the subacute phase of spinal cord injury (SCI), reactive astrocytes eventually migrated to the lesion epicenter and gradually compacted the infiltrated inflammatory cells and contracted the lesion area, and functional recovery was observed only in this repair phase. Selective deletion of the signal transducer and activator of transcription-3 (STAT3) in reactive astrocytes resulted in their limited migration associated with zinc signaling, markedly widespread damaged area and severe motor deficits. These results suggest that STAT3 is a key regulator of reactive astrocytes migration in the healing process after SCI, providing a beneficial aspect of reactive astrocytes after CNS injury.

Physiological significance of astrogliosis after CNS injury