Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice.
Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema. Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO) mice. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047. The increased MMP-2/9 protein expression in hippocampi of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occludens-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein expression increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein expression was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein.
Department of Physiology, Nanjing Medical University Nanjing, China.
Pinghui
P
Jie
Department of Physiology, Nanjing Medical University Nanjing, China.
Yujing
Y
Tian
Department of Physiology, Nanjing Medical University Nanjing, China.
Zhiwen
Z
Hong
Department of Physiology, Nanjing Medical University Nanjing, China.
Lin
L
Li
Department of Physiology, Nanjing Medical University Nanjing, China.
Libin
L
Zhou
Department of Physiology, Nanjing Medical University Nanjing, China.
Lei
L
Chen
Department of Physiology, Nanjing Medical University Nanjing, China.
Ling
L
Chen
brain edema; cerebral ischemia; matrix metalloproteinase; tight junction protein; transient receptor potential vanilloid 4