The influence of litter size on brain damage caused by hypoxic-ischemic injury in the neonatal rat

Hypoxic ischemia is a common cause of brain injury in the human neonate. This can be mimicked in the neonatal rat, but produces variable injury. The present study investigated the influence of litter size on the severity and variability of damage caused by hypoxic-ischemic injury in neonatal rats. Groups of 7-d-old pups from birth-sized litters (13-15 pups), or from litters culled to 10 on postnatal d 2, and 8- and 9-d-old pups from birth-sized litters, were exposed to common carotid artery occlusion and then, 3 h later, hypoxia (2 h 15 min, 8% oxygen). Damage was assessed histologically 72 h after injury, and graded (I-IV) according to severity. In nonculled litters, similar numbers of animals had each grade of injury. Most pups (70%) from culled litters had grade III or IV damage, and severity was significantly greater than in nonculled litters (p <0.001). Pups from culled litters were heavier (17.6 ± 0.4 g) than pups from nonculled litters (14.7 ± 0.3 g, p <0.0001). To determine whether this indicated that culled litters were more similar to older pups in their response to hypoxic-ischemic injury, we examined injury in 8- and 9-d-old pups of similar body weight to 7-d-old pups from culled litters. The severity and distribution of damage in the older pups was different from damage in the 7-d-old pups from culled litters. These data suggest that in 7-d-old rats, litter size influences damage caused by hypoxicischemic injury, and that the relationship between body weight, brain development, and susceptibility to hypoxic-ischemic injury is complex.