Strain Variability, Injury Distribution, and Seizure Onset in a Mouse Model of Stroke in the Immature Brain

Abstract

Neonatal stroke is an important cause of neurologic morbidity and cerebral palsy. Recently, we have determined that in postnatal day 12 CD1 mice unilateral carotid ligation alone results in seizures and brain injury. We have shown that, in this model, seizure scores correlate with brain injury scores. We have applied this model to another strain of mice to assess strain-related differences in vulnerability to seizures and brain injury after unilateral carotid ligation. Under isoflurane anesthesia, unilateral right-sided carotid ligation was performed in postnatal day 12 C3HeB/FeJ mice followed by a 4-hour period of observation in a 35°C incubator. Seizure scores and brain jury scores were assigned and compared to scores in mice receiving sham surgery. Timing of seizure onset and regional distribution of brain injury were compared in the CD1 and C3HeB/FeJ mice. Unilateral carotid ligation in postnatal day 12 C3HeB/FeJ mice resulted in seizure behavior and brain injury in some animals, with similar time to seizure onset and regional injury distribution, but affected a significantly smaller percentage of C3HeB/FeJ pups than that observed in postnatal day 12 CD1 mice, indicating strain-related vulnerability in this model.