CNS border macrophages in health and disease

Subdural central nervous system (CNS)-associated macrophages (CAMs), encompassing macrophages of the leptomeninges and perivascular spaces, serve as the primary immune sentinels at the CNS interfaces. These cells have been suggested to be indispensable for maintaining homeostasis and orchestrating responses in pathological states. Under physiological conditions, CAMs continuously remodel the CNS borders, impact cerebrospinal fluid dynamics, uphold immune surveillance, and regulate cerebral blood flow through intricate interactions with mural and stromal cells. In disease, their roles diversify, encompassing the generation of reactive oxygen species, the regulation of blood-brain barrier (BBB) integrity, and the coordination of the local immune response. This review synthesizes contemporary insights into the molecular heterogeneity and context-specific functions of subdural CAMs, while exploring innovative therapeutic strategies targeting these cells.