Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain injury.

Improvements in both obstetric and paediatric care have been responsible for a continuing reduction in mortality in extremely premature infants. However, higher survival rates have been at the expense of more long-term neurological damage. Various animal models have been developed to study the effect of hypoxic-ischemic insults on the brain. However, established models like the postnatal day 7 rat model represent damage found in term infants rather than in preterm infants of 24-28 weeks' gestation, and produce a severe form of injury resulting in high mortality rates. In this study we developed a reliable model of minor hypoxic-ischemic brain injury in postnatal day 3 rats. At this maturity, the pattern of damage represents that expected in a preterm infant suffering a non-lethal perinatal insult. We found that minor changes in duration of insult and both temperature and humidity produced wide fluctuations in the degree of injury observed. By maintaining strict control over experimental conditions including duration of insult, temperature and humidity, we produced a reliable model of minor injury primarily affecting all five areas of the cerebral cortex, and also the thalamus (area 7) and basal ganglia (area 8). Differences were significant compared to normal controls and sham-operated animals (p<0.05). These areas represent the primary motor, insular, visual and temporal cortices. The overall mortality rate in this study was 12.3%.