Figure 1.

Schematic representation of changes in blood-brain barrier (BBB) integrity and permeability in acute ischemic stroke (IS). In physical conditions, the selective permeability of the BBB is attributed to rare vesicles and negligible transcytosis in central nervous system (CNS) endothelial cells (ECs) and specialized tight junctions (TJ) between ECs. The major facilitator superfamily domain containing 2a (Mfsd2a) is selectively expressed in BBB-containing blood vessels and regulated by pericytes. Mfsd2a establishes a unique lipid environment that inhibits caveolae vesicle formation in CNS ECs to suppress transcytosis and ensure BBB integrity. In IS, the number of endothelial caveolae and caveolae-mediated transcytosis rates increase as early as 6 h after ischemia, macromolecular substances such as albumin can be transported through caveolae-mediated transcytosis, while TJ displayed profound structural defects only after 48 h. The increase of CNS endothelial vesicles is accompanied by a change of pericytes basement membrane coverage and the swelling of astrocytes’ end-feet and their mitochondria.