Resveratrol Attenuates the Blood-Brain Barrier Dysfunction by Regulation of the MMP-9/TIMP-1 Balance after Cerebral Ischemia Reperfusion in Rats
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The collapse of the blood-brain barrier (BBB) is one of the fundamental pathophysiology changes during cerebral ischemia reperfusion injury. Resveratrol has been recently reported to reduce cerebral ischemic damage by regulating the matrix metalloproteinase-9 (MMP-9). But, more direct evidence for the explanation of the BBB protected by resveratrol against cerebral ischemia reperfusion is still lacking. Therefore, the present study was aimed to investigate the regulation of BBB integrity by resveratrol after cerebral ischemia reperfusion and to determine the role of the MMP-9 and its endogenous inhibitor TIMP-1 balance in this process. Cerebral ischemia was induced by middle cerebral artery occlusion in rats. The BBB function was evaluated by brain water content and the Evans blue dye extravasation; the activities of MMP-9 and TIMP-1 were detected by using gelatin zymography analysis, and cellular apoptosis was examined by TUNEL staining. We confirmed that resveratrol reduced the cerebral ischemia reperfusion damage, brain edema, and Evans blue dye extravasation. Moreover, we found that resveratrol improved the balance of MMP-9/TIMP-1 in terms of their expressions and activities. A TIMP-1 neutralizing antibody reversed those neuroprotective effects of resveratrol. In conclusion, resveratrol attenuated the cerebral ischemia by maintaining the integrity of BBB via regulation of MMP-9 and TIMP-1.
KeywordsResveratrol Cerebral ischemia Blood-brain barrier Matrix metalloproteinase Tissue inhibitor of metalloproteinase
This work was supported by the National Natural Science Foundation of China (Grant No. 43411C1071), the Changjiang Scholars and Innovative Research Team in University (Grant IRT1053), and the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant 2012BA111B02). The authors greatly appreciate the help provided by Miss Yaoying Yu and thank Dr. Bairen Wang for carefully reading the manuscript.
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