Serial magnetic resonance imaging in a rat pup filament stroke model

Neonatal stroke is increasingly recognized in preterm and term infants but the ability to study this condition has been limited by the technical challenges in developing suitable animal models. In the current study we report the use of transient filament middle cerebral artery occlusion for 1.5 h in 10-day-old rat pups in which we were able to perform serial magnetic resonance imaging (MRI) studies. Serial MRI was performed immediately after the onset of stroke until 28 days after injury in an 11.7 T scanner using diffusion weighted and T2-weighted images. At 28 days the rat pups were sacrificed and standard histological stains were performed to validate stroke area. Serial behavioral assessments were also performed on the day of each imaging study. The anatomical distribution of stroke was similar to that expected from occlusion of the middle cerebral artery in adult models and represents a specific model of neonatal stroke in contrast to the commonly used model of carotid artery occlusion with 8% hypoxia. The initial stroke volume from MR measurements was 39% of the ipsilateral hemisphere at 0 h post-occlusion, reached a maximum at 24 h (44%) and then decreased in size (17%) with subsequent cavitation by 28 days. Infarction was more visible early with diffusion weighted imaging whereas T2-mapping provided more accurate infarct volumes at later time points. Despite the relatively large infarct volume, we saw little evidence of behavioral neurological deficit suggesting that this may also serve as a model of developmental plasticity and recovery.