This study aimed to investigate the effects of transient receptor potential vanilloid 4 (TRPV4) inhibition on blood-brain barrier (BBB) integrity and the expressions of caveolae structural
proteins caveolin-1 and
caveolin-2 in rats with focal
cerebral ischemia and reperfusion. BBB permeability was assessed by
Evans blue extravasation. The
mRNA and
protein expressions of
caveolin-1 and
caveolin-2 were determined by RT-PCR, Western blot and immunohistochemistry assays. We found that BBB permeability significantly increased and reaches its peak at 72 h of reperfusion in
cerebral ischemia-reperfusion rats and is able to be ameliorated by administration of
HC-067047, an antagonist of TRPV4. Additionally, it shows a significant upregulation of
caveolin-1 and
caveolin-2 expression in cerebral microvessels of ischemic tissue. However, treatment with
HC-067047 was shown to downregulate
caveolin-1 and
caveolin-2 expression during
cerebral ischemia-reperfusion. This study demonstrates that inhibition of TRPV4 ameliorates BBB leakage induced by
ischemia-reperfusion injury through the downregulation of
caveolin-1 and
caveolin-2.