Figure 5.

Early inhibition of AT1 by candesartan improves the blood-brain barrier (BBB) permeability and attenuates the disruption of BBB ultrastructrure. Twenty-month-old rats received laparotomy under isoflurane anesthesia in the presence or absence of candesartan pretreatment. BBB permeability was assessed by IgG expression in brain tissues and plasma levels of S100β. (A) Western blot analysis of IgG heavy chain (HC) and light chain (LC) expression indicated that candesartan reduced IgG-HC expression at 24 h after surgery (n = 6). (B) Serum S100β levels at 24 h after surgery. Enzyme-linked immunosorbent assay (ELISA) data revealed a significant increase in plasma S100β levels at 24 h post-surgery compared with sham, which was attenuated by candesartan pretreatment (n = 6). (C) Representative images of BBB ultrastructure from a coronal section through the hippocampal CA1 subfield (n = 4). Ultrastructure of the neurovascular unit was observed at 24 h after surgery using transmission electron microscopy. The capillary ultrastructure appeared nornal for the rats in the sham group. At 24 h postsurgery, the basal laminas partly collapsed (arrowhead), the perivascular spaces were enlarged. Swelling in astrocyte end-feet (*) and some swollen mitochodria (★) were also observed after surgery. Candesartan improves the above ultrastructure changes. L: lumen of blood vessel. Scale bar = 200 nm. *p < 0.05 vs. sham. ^#p < 0.05 vs. surgery.