RESUMEN
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.
Asunto(s)
Daño Encefálico Crónico/prevención & control , Lesiones Encefálicas/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Simvastatina/uso terapéutico , Animales , Química Encefálica/efectos de los fármacos , Química Encefálica/fisiología , Daño Encefálico Crónico/enzimología , Daño Encefálico Crónico/patología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/enzimología , Lesiones Encefálicas/patología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/enzimología , Isquemia Encefálica/patología , Mapeo Encefálico/métodos , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/enzimología , Arterias Cerebrales/patología , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Corteza Cerebral/fisiología , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/enzimología , Infarto Cerebral/etiología , Infarto Cerebral/patología , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/enzimología , Endotelio Vascular/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inmunohistoquímica/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Fármacos Neuroprotectores/uso terapéutico , Óxido Nítrico Sintasa/inmunología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo III , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: The spontaneously hypertensive stroke-prone rat (SHRSP) is an animal model for a complex form of cerebrovascular pathology. MRI provides an efficient and noninvasive tool for studying the time course of brain damage. The aim of this study was to gain new insights into the pathological phenomena responsible for the occurrence of brain injury in SHRSP with the use of the apparent diffusion coefficient of water (ADC), one of the most efficient MRI parameters for detecting brain abnormalities. To this end, the pattern of ADC variation observed in SHRSP was compared with that of focal ischemia induced in both SHRSP and Sprague-Dawley rats. METHODS: Four groups of animals were studied: SHRSP developing spontaneous brain lesions fed with a salt-loaded (n=15, group 1) or standard diet (n=3, group 2) and Sprague-Dawley rats (n=8, group 3) and SHRSP (n=8, group 4) with permanent middle cerebral artery occlusion. ADC maps and T2-weighted images of brains were performed by MRI. After the rats were killed, the brains were removed and histologically processed. RESULTS: There was no decrease in ADC during spontaneous stroke in the SHRSP fed with a normal or salt-enriched diet, while both the SHRSP and Sprague-Dawley rats with middle cerebral artery occlusion showed a marked decrease that lasted for 24 to 48 hours. CONCLUSIONS: Cerebral ischemia cannot be considered a major factor in the onset of spontaneous brain lesions in SHRSP, which show only vasogenic edema after the beginning of the damage with no evidence of metabolic impairment.