Chronic brain injury and behavioral impairments in a mouse model of term neonatal strokes

Stroke in term neonates remains a significant cause of long-term neurological morbidity. This study was designed to assess the relationships between ischemic stroke induced by permanent unilateral carotid ligation in P12 CD1 mice and the structural and functional outcomes in the young mice as a consequence. After P12 ischemic strokes, mice were behaviorally tested using accelerated rotorod, spontaneous alternation on a T-maze, open-field, and cylinder tests between P33 and P39. Brain injury was scored by histology at P40 with cresyl violet-stained coronal sections and computerized quantification of the ischemic injury. The ligation-injured mice were not different from controls on cylinder testing for asymmetric use of their forelimb, or on rotorod measures. In the spontaneous alternation task, however, injured mice demonstrated significantly lower rates of alternation indicating a deficit in working memory. Open-field testing repeated on two consecutive days revealed that the ligated mice were less active than the controls and that they failed to habituate to the open field environment between sessions indicating a learning deficit. Overall, our results demonstrate that ischemia induced by our neonatal stroke model produces behavioral deficits that are consistent with the brain injury.