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

Melatonin decreases matrix metalloproteinase‐9 activation and expression and attenuates... Abstract: 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Pineal Research Wiley

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

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References (44)

Publisher
Wiley
Copyright
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
ISSN
0742-3098
eISSN
1600-079X
DOI
10.1111/j.1600-079X.2008.00617.x
pmid
18624955
Publisher site
See Article on Publisher Site

Abstract

Abstract: 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.

Journal

Journal of Pineal ResearchWiley

Published: Nov 1, 2008

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