Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging

Abstract

The appearance and evolution of brain infarcts over 3 days following proximal occlusion of the left middle cerebral artery (MCA) in SHR rats were measured non-invasively by magnetic resonance imaging (MRI). Infarcts were clearly visible in coronal, T2 weighted brain sections, 24, 48 and 72 h after MCA occlusion in the left hemisphere, as areas of increased NMR signals. The infarcts were quantified by pixel counting in each section, the sum of 4 sections representing an accurate estimate of the total infarct size. The location and extent of infarction, determined by MRI, were found to be highly reproducible and correlated well with post-mortem histological and biochemical data. A neurological score, made every 24 h, paralleled the evolution of the infarct size, which culminated after 48 h. Pre- or post-treatment of MCA occluded rats with the dihydropyridine calcium antagonist PN 200-110 resulted in a substantial reduction of infarct size, determined by MRI 24, 48 and 72 h after infarction, compared to vehicle treated controls. These findings were corroborated by corresponding improvements of the neurological scores as well as histological and biochemical data. Post-treatment with nimodipine showed qualitatively similar effects. These results support the notion that calcium antagonists, through vascular and/or metabolic mechanisms, are effective in treating acute stroke. Since they were obtained in a chronic, relevant model of stroke with a method directly applicable also to humans, they should encourage further clinical studies with calcium antagonists.