| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6265352 | Brain Research | 2011 | 13 Pages |
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 2Â 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 24Â 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.
Research HighlightsâºLentivirus vector-mediated MMP-9shRNA infected the ependymal, endothelial and choroid plexus cells in brain after injection via intracerebroventricular. âºLV-mmp9shRNA silenced the expression of MMP-9 mRNA in the brain of rat in MCAO model. âºIt ameliorated BBB disruption and subsequently reduced vascular permeability and brain water content. âºIt significantly decreased the infarct volume, reduced the neurobehavioral deficits, and provided excellent neuroprotective effects.
