Immune System of the Ischemic Brain: Old Paradigms Revisited

The central nervous system was once viewed as immunologically privileged, but it is now recognized that brain-immune interactions are dynamic and critical. After central nervous system injury or disease, microglia and perivascular macrophages survey the damaged tissue, while diverse immune cells infiltrate through various barriers, driving neurovascular dysfunction and neuroinflammation. Depending on timing and phenotype, systemic immune responses can also promote brain repair and recovery. Recent studies show that brain-peripheral organ communication profoundly affects both injury progression and healing. These insights redefine the neurovascular-immune interface and the concept of the brain's immune system. This review examines immune cell infiltration and highlights emerging brain-peripheral circuits that regulate neuroinflammation and recovery after stroke.