Abstract
Activated NF-kappaB contributes to cerebral infarction by triggering a neuro-inflammatory response. Rats subjected to 90min middle cerebral artery occlusion developed a cortical infarct of 20+/-4% of hemispheric volume (n = 8). Treatment with the proteasome inhibitor CVT-634 resulted in a significantly smaller infarct of 13+/-2% (n = 7, p<0.01) and 12+/-2% (n = 8, p<0.001) of hemispheric volume at 1 day and 7 days, respectively. Since regional cerebral blood flows for the core and penumbral regions were not affected, we concluded that all animals received the same ischemic insult The reduction in infarction persisted for 7 days. This is the first indication that a proteasome inhibitor can reduce infarct volume in a focal model of cerebral ischemia.
MeSH terms
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Animals
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Cerebral Cortex / blood supply
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cerebral Cortex / pathology
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Cerebrovascular Circulation / drug effects
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Cysteine Endopeptidases / pharmacology*
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Cysteine Proteinase Inhibitors / pharmacology
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Dipeptides / pharmacology*
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Infarction, Middle Cerebral Artery / drug therapy*
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Laser-Doppler Flowmetry
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Male
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Multienzyme Complexes / pharmacology*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism*
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Neuroprotective Agents / pharmacology*
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Proteasome Endopeptidase Complex
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Rats
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Rats, Inbred SHR
Substances
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5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide
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Cysteine Proteinase Inhibitors
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Dipeptides
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Multienzyme Complexes
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NF-kappa B
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Neuroprotective Agents
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex