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.