Modeling the effect of anesthesia in pregnancy and impact on the fetal brain: Studies in rabbits

Pregnant women can be exposed to anesthesia for maternal (e.g., appendectomy) or fetal surgery (e.g., in utero repair of myelomeningocele). General anesthetics administered to the mother easily cross the placenta and reach the fetus. Previous preclinical studies, mainly using rodents, demonstrated that prenatal anesthesia exposure of the fetal brain could result in neuronal injury and behavioral impairments. However, these studies had several limitations and did not always reflect clinical conditions. Some of these limitations can be overcome by the fetal rabbit model. This model allows performing clinically relevant anesthesia in combination with maternal and fetal surgery. Various validated neurobehavioral assessments (for neonatal and juvenile rabbits) can be performed, and neuronal injury can be assessed by numerous histological outcomes, e.g., neuron density, proliferation, number of synapses. This chapter describes the general methodology and the specific methods and results of five research questions.