Bilateral Uterine Artery Ligation (BUAL): Placental Insufficiency Causing Fetal Growth Restriction and Cerebral Palsy

Abstract

Placental insufficiency is the leading cause of intrauterine growth restriction in the western world. The fetus, when exposed to a compromised environment, is vulnerable to a number of disorders later in life, as a consequence of the reduction in oxygen and nutrition during gestation and the resulting fetal growth restriction. These conditions include neurological disabilities such as cerebral palsy (CP), intellectual disability, epilepsy, and mental health issues in childhood (Autism and ADHD) and in later life (schizophrenia). Certainly, fetal growth restriction as a result of placental insufficiency has been strongly associated with adult onset disease including cardiovascular disease, diabetes, and stroke. Current therapeutic interventions are limited, and there are no standard therapies utilized which examine prevention of these disorders, in the face of a growth restricted fetus. In this regard, models that impact the intrauterine environment are vital to the development of preclinical phenotypes that mimic human conditions. In this case, our laboratory along with several others has developed a model of placental insufficiency with fetal growth restriction and a cerebral palsy phenotype as the outcome. The result is a model that reflects mild to moderate cerebral palsy and expresses the pathologic, radiologic, and functional deficits that closely reflect that of the human, and that persist into adulthood. In addition, our group and has shown that the inherent fetal growth restriction characteristics of this model exhibits evidence of later onset adult disease. The latter findings reflect the overlap of fetal growth restriction as a risk factor for cerebral palsy. This chapter provides an informative background and the methodologies required for the development and duplication of this model of placental insufficiency in the rodent.