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rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-12-20
pubmed:abstractText
Various studies on focal cerebral ischemic models have implicated the direct activation and expression of matrix metalloproteinases (MMPs), especially MMP-9, as a key orchestrator of blood-brain barrier (BBB) disruption. Moreover, studies have shown that MMP-9 siRNA can protect the BBB from ischemia/reperfusion injury. In the present study, we investigated the neuroprotective role of a lentivirus vector-mediated mmp-9shRNA following focal cerebral ischemia--specifically assessing whether LV-mmp9shRNA silencing of MMP-9 mRNA could ameliorate BBB disruption and in turn reduce vascular permeability, neuronal cell death, and neurobehavioral deficits. Treatment was given 2 weeks prior to surgery using a lentivirus-mediated vector. Surgery was conducted using the established middle cerebral artery occlusion (MCAO) model in rats, while outcomes were measured 24 h after injury. Our results demonstrated a significant reduction in brain infarction volume, brain water content, and neurobehavioral deficits following LV-mmp9shRNA treatment. Additionally, Evans blue and IgG extravasation were reduced, MMP-9 mRNA expression was silenced, and Western blot analysis revealed a decreased expression of MMP-9 and VEGF with an increased expression of occludin and collagen IV in brain tissues. This suggests that successful delivery of LV-mmp9shRNA may ameliorate ischemic brain injury by preserving structural integrity and improving functional outcome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
1367
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
347-59
pubmed:meshHeading
pubmed-meshheading:20950592-Analysis of Variance, pubmed-meshheading:20950592-Animals, pubmed-meshheading:20950592-Blood-Brain Barrier, pubmed-meshheading:20950592-Cell Line, Transformed, pubmed-meshheading:20950592-Cells, Cultured, pubmed-meshheading:20950592-Disease Models, Animal, pubmed-meshheading:20950592-Evans Blue, pubmed-meshheading:20950592-Gene Expression Regulation, pubmed-meshheading:20950592-Gene Transfer Techniques, pubmed-meshheading:20950592-Infarction, Middle Cerebral Artery, pubmed-meshheading:20950592-Lentivirus, pubmed-meshheading:20950592-Male, pubmed-meshheading:20950592-Matrix Metalloproteinase 9, pubmed-meshheading:20950592-RNA, Messenger, pubmed-meshheading:20950592-RNA, Small Interfering, pubmed-meshheading:20950592-Rats, pubmed-meshheading:20950592-Rats, Sprague-Dawley, pubmed-meshheading:20950592-Single-Blind Method, pubmed-meshheading:20950592-Tetrazolium Salts, pubmed-meshheading:20950592-Trauma Severity Indices
pubmed:year
2011
pubmed:articleTitle
Lentivirus-mediated transfer of MMP-9 shRNA provides neuroprotection following focal ischemic brain injury in rats.
pubmed:affiliation
Department of Anatomy and Embryology, Peking University Health Science Center, Beijing 100191, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't