Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats

Yu Chang Hung, Tsung Ying Chen, E. Jian Lee, Wan Ling Chen, Sheng Yang Huang, Wei Ting Lee, Ming Yang Lee, Hung Yi Chen, Tian Shung Wu

研究成果: Article同行評審

46 引文 斯高帕斯(Scopus)

摘要

We have previously shown that melatonin reduces postischemic rises in the blood-brain barrier (BBB) permeability and improves neurovascular dysfunction and hemorrhagic transformation following ischemic stroke. It is known that activation of the matrix metalloproteinases (MMPs) plays a crucial role in the pathogenesis of brain edema and hemorrhagic transformation after ischemic stroke. We, herein, investigated whether melatonin would ameliorate MMP-2 and MMP-9 activation and expression in a rat model of transient focal cerebral ischemia. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery (MCA) occlusion using an intraluminal filament. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhage within infarcts were measured, and neurological deficits were scored. The activity and expression of MMP-2 and MMP-9 were determined by zymography, in situ zymography and Western immunoblot analysis. Cerebral ischemia-reperfusion induced increased pro-MMP-9 and MMP-9 activity and expression 24 hr after reperfusion onset. Relative to controls, melatonin-treated animals, however, had significantly reduced levels in the MMP-9 activity and expression (P < 0.01), in addition to reduced brain infarct volume and hemorrhagic transformation as well as improved sensorimotor neurobehavioral outcomes. No significant change in MMP-2 activity was observed throughout the course experiments. Our results indicate that the melatonin-mediated reductions in ischemic brain damage and reperfusion-induced hemorrhage are partly attributed to its ability to reduce postischemic MMP-9 activation and increased expression, and further support the fact that melatonin is a suitable as an add-on to thrombolytic therapy for ischemic stroke patients.

原文English
頁(從 - 到)459-467
頁數9
期刊Journal of Pineal Research
45
發行號4
DOIs
出版狀態Published - 2008 十一月 1

All Science Journal Classification (ASJC) codes

  • 內分泌

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