Calycosin regulates astrocyte reactivity and astrogliosis after spinal cord injury by targeting STAT3 phosphorylation.

BACKGROUND

Astrocytes are the most populous glial cells in the central nervous system (CNS), which can exert detrimental effects through a process of reactive astrogliosis. Our previous study has indicated the potential effect of Calycosin in preventing spinal cord injury (SCI). This study aims to investigate the mechanism by which calycosin regulates the polarization of A1 astrocytes, a neurotoxic subtype of reactive astrocytes, in SCI models.

MATERIALS AND

METHODS

The SCI model was induced by applying mechanical compression to the spinal cord using vascular clamps. A1 astrocyte differentiation was induced by treating astrocytes with microglia supernatant obtained after Lipopolysaccharide (LPS) stimulation. Key protein expression levels were analyzed by Western blotting, and astrocyte markers such as CS56, GFAP, C3, S100A10 were assessed through immunofluorescence staining.

RESULTS

Calycosin treatment significantly reduced glial scar formation and C3 expression in SCI rats. However, S100A10 expression remained unchanged. Further analysis showed that Calycosin inhibited A1 astrocyte activation, migration, and invasion, which was associated with STAT3 phosphorylation. Calycosin downregulated p-STAT3 levels in both A1 astrocytes and SCI rats. These effects were reversed by Colivelin (a STAT3 activator) in A1 astrocytes.

CONCLUSION

Calycosin treatment can modulate p-STAT3 expression, thereby altering the functionality of astrocytes during the recovery phase and positively impacting the treatment and rehabilitation of SCI.