Magnetic resonance imaging as a surrogate measure for histological sub-chronic endpoint in a neonatal rat stroke model

INTRODUCTION It is becoming increasingly recognized that CNS immaturity at birth affects ischemic injury and recovery, and that the consequences of neonatal stroke need to be studied using age-appropriate focal stroke models. The inclusion of magnetic resonance imaging (MRI) as a surrogate measure of stroke progression has provided useful information in adult models, but the benefit for neonatal stroke studies is yet to be established. METHODS Postnatal 7-day (P7) rats were subjected to a 3-h transient occlusion of the middle cerebral artery (MCA) which was produced either by inserting a filament via the external carotid artery or via the internal carotid artery. MRI was used to delineate the size and pattern of injury acutely, during MCA occlusion, and 7 days following reperfusion. RESULTS The size of the diffusion-weighted (DW) MRI-detectable injury during MCA occlusion was similar following both surgical procedures and resulted in histological lesions 7 days later in all animals. The extent of spontaneous recovery in individual animals varied substantially 7 days later within each group, as was depicted by a combination of DW- and T2W-MRI and confirmed by the corresponding histology. CONCLUSIONS The ability of MRI to provide accurate information on the size of histological outcome at 7 days after neonatal focal transient ischemia suggests that MRI is useful as an intermediate surrogate measure of injury progression in long-term neonatal stroke studies.