Inhibition of transient receptor potential vanilloid 4 decreases the expressions of caveolin‐1 and caveolin‐2 after focal cerebral ischemia and reperfusion in rats |
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| Authors: | Hui Xie Wei‐cheng Lu |
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| Institution: | 1. Department of Histology and Embryology, College of Basic Medicine, Shenyang Medical College, Shenyang, ChinaThe first two authors contributed equally to this work and should be considered co‐first authors;2. Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, ChinaThe first two authors contributed equally to this work and should be considered co‐first authors |
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| 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. |
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| Keywords: | blood– brain barrier caveolin‐1 caveolin‐2 cerebral ischemia reperfusion transient receptor potential vanilloid 4 |
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