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Objective·To investigate whether the inactivation of Wnt7/β-catenin signaling causes the destruction of the blood-brain barrier (BBB) in cerebrovascular endothelial cells after ischemic stroke, and investigate whether endoplasmic reticulum stress bursts mediates the inhibition of Wnt7/β-catenin pathway.Methods·The model of middle cerebral artery occlusion (MCAO) in mice was established by a monofilament nylon suture with a round tip, which was used to temporarily occlude the middle cerebral artery for 60 min. MCAO model mice were intraperitoneally injected with the endoplasmic reticulum stress blocker 4-phenylbutyric acid (4-PBA) as 4-PBA+MCAO group. Sham surgery group (Sham group) was set. Twenty-four hours after MCAO, Evans blue (EB) was used to measure the BBB permeability. The brain water content was calculated by dry-wet weight ratio, and the adhesion of cerebrovascular endothelial cells and pericytes in mice was measured by immunofluorescence. Human brain microvascular endothelial cells (HBMECs) were used to establish an oxygen and glucose deprivation (OGD) model for 4 h, and then cultured with 4-PBA for 24 h. Cells were divided into blank control group, OGD group, and OGD+4-PBA group for CCK-8 assay to determine the cell viability. FITC-labeled bovine serum albumin (FITC-BSA) was used to detect the cell permeability. The secretion of platelet-derived growth factor β (PDGF-β) was measured by ELISA. Fluo-3 AM fluorescence probe was used to detect the fluorescence intensity of cells to assess intracellular Ca2+ concentration, and reactive oxygen species (ROS) content was measured by CM-H2DCFDA fluorescence probe to clarify the endoplasmic reticulum stress state. Western blotting was used to examine the expression of connexins, including zonula occludens-1 (ZO-1) and claudin-5, the expression of endoplasmic reticulum stress proteins, including CCAAT/enhancer-binding protein homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and cysteine-containing aspartate-specific proteases-12 (Caspase-12), and the expression of Wnt7/β-catenin in HBMECs.Results·Compared with the Sham group, the brain water content of the infarction area of mice increased after MCAO, and the exudation of EB increased significantly (both P