title: Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion.
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.
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
authors.forename: Haolin
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Mang
authors.affiliation: Department of Neurosurgery, First Hospital, Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Xu
keywords: Evans blue; GM6001; blood-brain barrier; claudin-5; gelatinases; junction protein; matrix metalloproteinase; middle cerebral artery occlusion; neural regeneration; occludin; permeability; reperfusion injury