Quantitative temporal profiles of penumbra and infarction during permanent middle cerebral artery occlusion in rats

The basic premise of neuroprotection in acute stroke is the presence of salvageable tissue, but the spatiotemporal volume profiles of the penumbra and infarction remain poorly defined in preclinical animal models of acute stroke used to evaluate therapies for clinical application. Our aim was to define these profiles using magnetic resonance imaging (MRI) quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) for dual-parameter voxel analysis in the rat suture permanent middle cerebral artery occlusion (pMCAO) model. Eleven male Sprague Dawley rats were subjected to pMCAO with MRI measurements of quantitative CBF and ADC at baseline, over the first 4 h (n=9) and at 7, 14, and 21 days (n=4). Voxel analysis of CBF and ADC was used to characterize brain tissue ischemic transitions. Penumbra, core, and hyperemic infarction volumes were significantly elevated (P<0.05) and unchanged over the first 4 h of pMCAO while the total lesion volume progressively rose. At 7, 14, and 21 days, tissue compartment transitions reflected infarction, tissue cavitation, and selective ischemic neuronal necrosis. Anatomical distribution of penumbra and core revealed marked heterogeneity with penumbra scattered within core and penumbra persisting even after 4 h of permanent MCAO.