Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion |
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Authors: | Haolin Xin Wenzhao Liang Jing Mang Lina Lin Na Guo Feng Zhang Zhongxin Xu |
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Institution: | (Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China) ; |
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Abstract: | Gelatinases matrix metalloproteinase-2 and matrix metalloproteinase-9 have been shown to mediate claudin-5 and occludin degradation, and play an important regulatory role in blood-brain barrier permeability. This study established a rat model of 1.5-hour middle cerebral artery occlusion with reperfusion. Protein expression levels of claudin-5 and occludin gradually decreased in the early stage of reperfusion, which corresponded to the increase of the gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. In addition, rats that received treatment with matrix metalloproteinase inhibitor N-(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpenthanoyl]-L-tryptophan methylamide (GM6001) showed a significant reduction in Evans blue leakage and an inhibition of claudin-5 and occludin protein degradation in striatal tissue. These data indicate that matrix metalloproteinase-2 and matrix metalloproteinase-9-mediated claudin-5 and occludin degradation is an important reason for blood-brain barrier leakage in the early stage of reperfusion. The leakage of the blood-brain barrier was present due to gelatinases-mediated degradation of claudin-5 and occludin proteins. We hypothesized that the timely closure of the structural component of the blood-brain barrier (tight junction proteins) is of importance. |
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Keywords: | gelatinases matrix metalloproteinase claudin-5 occludin blood-brain barrier Evans blue middle cerebral artery occlusion reperfusion injury GM6001 junction protein permeability neural regeneration |
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