Background & Objectives: Spinal cord injury (SCI) abruptly alters the protease microenvironment, including elevations in thrombin capable of activating Protease Activated Receptor 1 (PAR1). PAR1 activation in astrocytes promotes pro-inflammatory and neurotoxic responses that hinder neural repair. Previous studies using PAR1 knockout mice demonstrated that knockout of the PAR1 gene reduces reactive astrogliosis and inflammation while preserving neurons and axonal integrity (Radulovic et al., 2016; Kim et al., 2021). Building on these findings, we employed a thoracic compression SCI model (T8–T9) in adult female C57BL6J mice to test whether pharmacological PAR1 antagonism could similarly sway astrocytes toward pro-repair states and thereby remodel the injury microenvironment.
Methods: The PAR1 antagonist (SCH79797) was delivered following thoracic compression (T8-T9) SCI in adult female C57BL6J mice. Immunophenotyping was completed to quantify astrocyte markers, including GFAP in addition to pro-repair markers (EMP1, S100A10) and a pro-inflammatory marker (C3D).
Results: PAR1 antagonism was associated with a downregulation of astrocytic pro-inflammatory signatures and concomitant upregulation of pro-repair markers.
Conclusion & Implications: Our findings suggest that PAR1 antagonism may promote astrocyte compartment skewing from inflammatory states toward a pro-repair phenotype, which could in turn facilitate neural regeneration. Integrating interventions targeting PAR1 with precise cell-phenotype mapping could unlock new therapeutic pathways to reprogram glial behavior and optimize CNS regeneration after injury.
