Matrix metalloproteinase inhibitor KB-R7785 attenuates brain damage resulting from permanent focal cerebral ischemia in mice.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix. MMP-9 and MMP-2 have been implicated in brain injury formation. The authors examined the effect of MMP inhibitor KB-R7785 on brain infarct formation resulting from permanent focal cerebral ischemia in mice. Ischemia was induced by intraluminal middle cerebral artery occlusion (MCAO) in mice under halothane anesthesia. Zymography was conducted to measure the MMPs activity in ischemic brain tissues. Injection of KB-R7785 (100 mg/kg) 30 min before MCAO significantly decreased both MMP-9 activity and infarct volume determined at 24 h. In addition, KB-R7785 injected twice at 1 and 4.5 h after MCAO significantly decreased infarct volume. These results indicate that KB-R7785 has a protective efficacy against focal cerebral ischemia, and our data provide further evidence that MMP-9 contributes to brain infarct formation.
Jiang
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X
Stroke and Brain Protection Laboratory, Research Institute, National Cradiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Osaka, Japan.
Namura
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S
Nagata
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I
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology*; D002544:Cerebral Infarction / Q000201:enzymology / Q000473:pathology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D011480:Protease Inhibitors / Q000494:pharmacology*
D006877:Hydroxamic Acids; C107086:KB R7785; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D005998:Glycine