Pathophysiological Role of Perivascular Macrophages in Blood-Brain Barrier Dysfunction Induced by Cerebral Hypoperfusion in Mice.

This study investigated the role of perivascular macrophages (PVMs), localized alongside the brain vasculature, in blood-brain barrier (BBB) dysfunction induced by reduced cerebral blood flow (CBF). Using a mouse model of bilateral carotid artery stenosis (BCAS) to examine cerebral hypoperfusion, the effects of pharmacological depletion of PVM-enriched macrophage populations were examined using clodronate liposomes. The results demonstrated that while cerebral hypoperfusion significantly increased BBB permeability, depletion of PVM-enriched macrophage populations attenuated this leakage. Mechanistic analyses suggested that PVM-associated responses may be linked to reduced pericyte marker expression, astrocyte activation, and increased MMP-2/9 expression. Furthermore, depletion of PVM-enriched macrophage populations inhibited the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. These findings suggest that PVM-enriched macrophage populations are involved in early BBB dysfunction following cerebral hypoperfusion, possibly through changes in pericyte-associated vascular integrity, astrocyte activation, and MMP-2/9-related tight junction remodeling. These results provide insight into vascular inflammatory mechanisms that may contribute to hypoperfusion-associated BBB dysfunction and later small vessel pathology.