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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00141/full |
| _version_ | 1819138451377750016 |
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| author | Pinghui eJie Yujing eTian Zhiwen eHong Lin eLi Libin eZhou Lei eChen Ling eChen |
| author_facet | Pinghui eJie Yujing eTian Zhiwen eHong Lin eLi Libin eZhou Lei eChen Ling eChen |
| author_sort | Pinghui eJie |
| collection | DOAJ |
| description | 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 in hippocampus of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occluden-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein 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. |
| first_indexed | 2024-12-22T11:06:59Z |
| format | Article |
| id | doaj.art-3b2c72a3a8264f2fb54b81b1b99f0e26 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T11:06:59Z |
| publishDate | 2015-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3b2c72a3a8264f2fb54b81b1b99f0e262022-12-21T18:28:16ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-04-01910.3389/fncel.2015.00141138441Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion micePinghui eJie0Yujing eTian1Zhiwen eHong2Lin eLi3Libin eZhou4Lei eChen5Ling eChen6Nanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityBrain 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 in hippocampus of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occluden-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein 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.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00141/fullBrain Edemacerebral ischemiamatrix metalloproteinaseTight junction proteinTransient receptor potential vanilloid 4 |
| spellingShingle | Pinghui eJie Yujing eTian Zhiwen eHong Lin eLi Libin eZhou Lei eChen Ling eChen Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice Frontiers in Cellular Neuroscience Brain Edema cerebral ischemia matrix metalloproteinase Tight junction protein Transient receptor potential vanilloid 4 |
| title | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| title_full | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| title_fullStr | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| title_full_unstemmed | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| title_short | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| title_sort | blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
| topic | Brain Edema cerebral ischemia matrix metalloproteinase Tight junction protein Transient receptor potential vanilloid 4 |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00141/full |
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