Long-Term Evaluation Of Motor Function And Learning-Memory Ability In A 3-Day-Old Ischemic Brain Injury Rat Model

To evaluate the histopathological changes, physical development and long term motor and learning-memory ability of a 3-day-old rat brain injury model. Postnatal day-3 male Sprague-Dawley rats were randomly assigned to experimental group induced by ligation of bilateral carotid arteries, and sham-operated control group (48 rats/group). At 1 day after the procedure and 3 weeks old, we used hematoxylin-eosin stain, myelin related protein immunohistochemistry, pre-oligodendrocyte marker O4 and TUNEL double immunofluorescence stain to investigate the pathological changes. Inspections of physical development were made after operation until 3 weeks old. Motor activity and coordination of the rats were evaluated by four sensorimotor tests between 3 to 6 weeks old. Learning and memory ability were tested by Morris water maze between 7 to 13 weeks old. The survival rate was 100% (48/48) in the control group and 68.8% (33/48) in the experimental group 24 hours after operation. Pathological changes including periventricular leukoaraiosis, dilated ventricles, and pre oligodendrocyte apoptosis. The expression of myelin basic protein was reduced at 3 weeks old. Rats in the experimental group showed decreased weight gain (P<0.05), poor motor ability and decreased maintenance of balance (P<0.05) and learning-memory defects compared with rats in the control group (P<0.05). Our rat model revealed a preferential occurrence of brain damage which is similar to preterm infant, and confirmed the early outcome is delayed growth development during childhood. The long term outcome including motor and learning-memory ability defect will persist until adulthood.