Repetitive intermittent hypoxia-ischemia and brain damage in neonatal rats

OBJECTIVE To know the effect of brief-repetitive intermittent hypoxia-ischemia on the development of perinatal brain damage. STUDY DESIGN Seven-day-old Wistar rats underwent ligation of the unilateral common carotid artery. The animals were allocated to three groups (n=12 in each group) and exposed to 8% oxygen as follows: group A: continuous exposure for 180 min; group B: continuous exposure for 90 min; and group C: 10 min of exposure repeated at 10-min intervals over a period of 180 min (total exposure time, 90 min). Seventy-two hours after exposure to hypoxia, the cerebral cortex was examined to assess the degree of neuronal necrosis and brain damage was classified into four grades of severity, 0-3. To evaluate the extent of brain damage, we used immunohistochemical staining with TIB-128 antibody, which reacts to MAC-1 antigen specific to microglia, and observed the glial reaction in the cerebral cortex, hippocampus, thalamus, and striatum. RESULTS All the brain damage observed in groups A-C occurred on the side where the ligation was performed. The most severe damage was found in group A animals, of which seven showed significant neuronal necrosis, having a grade 2 or more advanced lesion. In group B, neuronal necrosis was modest, with only one animal having a grade 2 lesion. In group C, a significant neuronal necrosis was found in six animals despite having the same period of hypoxic exposure as those in group B. MAC-1 positive cells appeared in the cerebral cortex of histologically damaged animals and extended to the hippocampus, thalamus, and striatum in severely damaged animals from groups A, B, and C. CONCLUSION Examination of the neonatal rat model suggested that repetitive and intermittent, rather than continuous hypoxia-ischemia, causes pronounced damage in the immature brain.