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

• Published in: Neuropathology Vol. 38; no. 4; pp. 337 - 346
• Main Authors: Xie, Hui, Lu, Wei‐cheng
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.08.2018; Wiley Subscription Services, Inc
• Subjects: Blood-brain barrier; Caveolae; Caveolin; caveolin‐1; caveolin‐2; cerebral ischemia reperfusion; Extravasation; Immunohistochemistry; Ischemia; Membrane permeability; mRNA; Permeability; Reperfusion; Rodents; Structural proteins; Transient receptor potential proteins; transient receptor potential vanilloid 4; blood-brain barrier; caveolin-1; transient receptor potential vanilloid 4; cerebral ischemia reperfusion; caveolin-2
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/neup.12469

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.