The study by O’shea et al. (2024) investigated the origin and reprogramming of reactive astrocytes that form around lesions in the central nervous system (CNS) after spinal cord injury (SML) or stroke (CVA) in mice. The authors found that most of these reactive astrocytes, which form a protective border around the lesion, are derived from mature local astrocytes that undergo a process of dedifferentiation, proliferation, and transcriptional reprogramming.
This transcriptional reprogramming involves decreased expression of molecules associated with interaction with neurons and an increase in expression of molecules related to wound healing, microbial defense, and interaction with connective tissue cells and the immune system. The resulting wound-repairing astrocytes share morphological and transcriptional characteristics with perivascular glial limitans astrocytes, which form a protective barrier around the healthy CNS.
In summary, this study deepens the understanding of the response of astrocytes to CNS lesions, with important implications for the development of targeted therapies for recovery after SCI and CVA. The discovery that reactive astrocytes are derived mainly from mature local astrocytes and the identification of their unique transcriptional characteristics open new perspectives for therapeutic interventions aimed at modulating the response of astrocytes to lesions, promoting CNS repair and functional recovery.
Reference:
The’SHEA, Timothy M. et al. Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice. Nature Neuroscience, v. 27, pp. 1562-1575, 2024.
