| Selective MMP-inhibition with Ro 28-2653 in acute experimental stroke--a magnetic resonance imaging efficacy study. | |
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MedLine Citation:
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PMID: 20971083 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Blood-brain-barrier (BBB) breakdown due to matrix metalloproteinase (MMP) activity following stroke is often associated with cerebral edema, larger infarct volumes and bad outcome. In the present study we examined a novel MMP-inhibitor (Ro 28-2653) with high selectivity for MMP2, MMP9 and membrane type 1-MMP in an acute stroke model comparing two different treatment regimens. We subjected rats to 90 min of focal cerebral ischemia followed by 3 days or 7 days of reperfusion, respectively, using the middle cerebral artery (MCA) filament occlusion technique. Ro 28-2653 was administered daily in a vehicle solution for 2 days or 6 days after ischemia, respectively. We assessed the behavior with a functional neuroscore and infarct volumes as well as blood-brain-barrier (BBB) breakdown with magnetic resonance imaging (MRI) after 3 and 7 days. Infarct edema volumes, BBB breakdown and behavior at 3 days were significantly attenuated in rats treated for 2 days with Ro 28-2653 as compared to vehicle and untreated controls. After 6 days of treatment however, infarct and BBB breakdown volumes as well as behavior did not differ significantly between the groups at 7 days. The new high selective MMP-inhibitor Ro 28-2653 significantly reduced brain injury only when administered in the first 2 days after focal cerebral ischemia. Prolonged treatment for 6 days did not show any beneficial effects possibly due to interference with protective restorative processes. |
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Authors:
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S Nagel; P V Heinemann; S Heiland; J Koziol; H Gardner; S Wagner |
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Publication Detail:
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Type: Journal Article Date: 2010-10-21 |
Journal Detail:
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Title: Brain research Volume: 1368 ISSN: 1872-6240 ISO Abbreviation: Brain Res. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 264-70 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Neurology, University of Heidelberg, Heidelberg, Germany. |
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