The role of astrocyte-derived extracellular vesicles in cellular microenvironment remodeling after spinal cord injury: A study based on quantitative proteomics analysis

After spinal cord injury (SCI), astrocytes (AS), the most abundant glial cells in the central nervous system, closely interact with other nerve cells. The precise mechanism by which astrocytes remodel the cellular microenvironment (CME) remains unclear; however, the extracellular vesicles (EVs) they release may facilitate communication between cells by transporting biological macromolecules. This study aimed to elucidate the role of astrocyte-derived EVs in modulating CME after SCI. An in vitro model of reactive astrocytes (RA) was developed under simulated SCI conditions, followed by proteomic analysis of EVs isolated from RA and AS. Differential protein expression was assessed using quantitative proteomics, complemented by gene set enrichment analysis to elucidate the associated biological functions. Our results indicate that AS-EVs provide neuroprotective benefits by attenuating microglial activation, decreasing neuronal apoptosis, promoting axonal growth, and facilitating the maturation of oligodendrocyte precursor cells, thereby improving motor function recovery in murine models. Conversely, RA-EVs exhibited deleterious effects, exacerbating inflammation and impeding functional recovery. CC Motif Chemokine Ligand 7 (CCL7) was identified as a critical secretory protein mediating these adverse effects. These findings elucidate the neuroprotective and regenerative mechanisms mediated by astrocyte-derived EVs, highlighting the therapeutic potential of CCL7-targeted interventions in promoting recovery after SCI.