Establishment of intrauterine hypoxic-ischemic brain damage model in near term fetal rabbits

AIM: To establish intrauterine hypoxic-ischemic brain damage (HIBD) model in near term fetal rabbits at 29 d gestation age for the investigation of the pathogenesis and treatment of newborn HIBD. METHODS: Twenty-four pregnant New Zealand white rabbits at 29th gestational day were chosen for this project. Under combined general anesthesia and spinal anesthesia, a 4F Fogarty arterial embolectomy catheter was introduced into the left femoral artery. The blood supply of uterus in experiment group was blocked by inflating the catheter balloon with 0.3 mL saline for 20 min, 25 min, 28 min, 30 min and 40 min (n=4 for each experimental time group). The catheter balloon was not inflated in control group (n=4). All pregnant rabbits were subject to cesarean section 24 h after the experimental procedure to induce hypoxia-ischemia to the fetus. The general conditions of the newborn rabbits were recorded, and the neurobehavioral damage and histology of the brain tissue were assessed. RESULTS: During the entire procedure, the pregnant rabbits had stable vital signs, no hypoxia happened,and had a good tolerance to the anesthesia program. When the balloon was inflated, the pulses of right femoral artery disappeared and the right leg blood pressure became non-detectable in experimental groups. In contrast, no fluctuation of the right leg blood pressure in control group (P>0.05) was observed. Intrauterine hypoxia-ischemia caused neonatal and fetal rabbit death, neurobehavioral damage and brain cell death. When the balloon was inflated for 20 min, all fetal rabbits were alive and had no obvious neurologic damage. For 25~28 min, the stillbirth rates were 12.9% and 40.6%, respectively, while the live neonatal rabbits manifested neurobehavioral damage, edema neural cells, activated microglia cells and apoptotic brain cells. When blocking time beyond 30 min, above 80% fetal rabbits died. CONCLUSION: Continuous blockage of uterine blood supply in pregnant rabbits causes neonatal rabbit death, neurobehavioral damage and brain cell death. Different blocking time arouses different levels of brain damage. Continuous blockage of uterine blood supply for 25-28 min can establish fetal generalize hypoxic-ischemic brain damage rabbit model, which is a good animal model for the investigation of newborn HIBD.