Inhibition of transient receptor potential vanilloid 4 decreases the expressions of caveolin-1 and caveolin-2 after focal cerebral ischemia and reperfusion in rats.

Abstract

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.