Spinal cord injury triggers specialized astrocytes distant from the damage site to secrete CCN1, a matricellular protein that fine-tunes nearby microglia to efficiently clear lipid-rich myelin debris. Without astrocyte-derived CCN1, microglia become dysregulated—accumulating cellular debris internally, developing abnormal lipid metabolism, and forming fewer protective lipid droplets. The CCN1 protein binds to microglial SDC4 receptors, enabling proper lipid storage and debris processing critical for tissue repair. This astrocyte-microglia communication represents a sophisticated quality control system where distant astrocytes coordinate local cleanup crews to restore white matter integrity. The finding challenges the traditional view of spinal cord injury as purely localized damage, revealing instead a networked repair response involving cells far from the injury epicenter. For neurological recovery, this suggests therapeutic targets beyond the lesion itself. The CCN1-SDC4 signaling axis could potentially be enhanced pharmacologically to improve debris clearance in various white matter diseases, from multiple sclerosis to stroke. However, translation from mouse models to human spinal injuries requires validation, and the optimal timing for such interventions remains unclear given the dynamic nature of post-injury astrocyte states.