Abstract
Objective:
In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat.
Methods and results:
Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats.
Conclusions:
Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.
MeSH terms
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Animals
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Brain Chemistry / drug effects
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Brain Chemistry / physiology
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Brain Damage, Chronic / enzymology
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Brain Damage, Chronic / pathology
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Brain Damage, Chronic / prevention & control*
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Brain Injuries / complications
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Brain Injuries / drug therapy*
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Brain Injuries / enzymology
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Brain Injuries / pathology
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Brain Ischemia / complications
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Brain Ischemia / drug therapy*
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Brain Ischemia / enzymology
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Brain Ischemia / pathology
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Brain Mapping / methods
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Cerebral Arteries / drug effects
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Cerebral Arteries / enzymology
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Cerebral Arteries / pathology
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Cerebral Cortex / blood supply
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Cerebral Cortex / drug effects
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Cerebral Cortex / pathology
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Cerebral Cortex / physiology
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Cerebral Infarction / drug therapy
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Cerebral Infarction / enzymology
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Cerebral Infarction / etiology
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Cerebral Infarction / pathology
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Disease Models, Animal
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / pathology
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Immunohistochemistry / methods
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Magnetic Resonance Imaging / methods
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Male
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Neuroprotective Agents / therapeutic use
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Nitric Oxide Synthase / immunology
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type III
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Rats
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Rats, Sprague-Dawley
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Simvastatin / therapeutic use*
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Up-Regulation / drug effects
Substances
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Neuroprotective Agents
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Simvastatin
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type III
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Nos3 protein, rat