Astrocytes in Multiple Sclerosis: Getting to the Core

Astrocytes are increasingly recognized as key regulators of multiple sclerosis (MS) pathogenesis, known to actively influence neuroinflammation, blood–brain barrier integrity, leukocyte recruitment, glial scar formation, and tissue repair. Evidence from both MS and its animal models demonstrates substantial astrocyte heterogeneity, exerting either pathogenic or neuroprotective functions depending on the local microenvironment. In this review, we discuss the diverse roles of astrocytes in MS, with particular focus on signaling pathways that govern astrocyte responses during chronic neuroinflammation. We further explore the growing evidence that astrocytes within chronic active lesion cores are not merely passive structural cells, but instead may be involved in immune regulation, survival signaling, and tissue maintenance. Collectively, these findings support a revised view of astrocytes as regulators of lesion dynamics and CNS homeostasis during MS. A deeper understanding of astrocyte heterogeneity and the signaling networks that control astrocyte function may reveal novel therapeutic opportunities to limit neurodegeneration and disease progression.