Neural Regeneration Research ›› 2012, Vol. 7 ›› Issue (31): 2405-2412.

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Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion

Haolin Xin1, Wenzhao Liang1, Jing Mang1, Lina Lin2, Na Guo1, Feng Zhang3, Zhongxin Xu1   

  1. 1 Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
    2 Department of Neurosurgery, First Hospital, Jilin University, Changchun 130021, Jilin Province, China
    3 College of Life Science, Jilin University, Changchun 130012, Jilin Province, China
  • Received:2012-08-08 Revised:2012-10-13 Online:2012-11-05 Published:2012-11-05
  • Contact: Zhongxin Xu, Doctoral supervisor, Professor,Department of Neurosurgery,China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China xuzhongxin999@yahoo.com.cn
  • About author:Haolin Xin☆, Studying for doctorate, 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]-Ltryptophan 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.

Key words: gelatinases, matrix metalloproteinase, claudin-5, occludin, blood-brain barrier, Evans blue, middle cerebral artery occlusion, reperfusion injury, GM6001, junction protein, permeability, neural regeneration