Chronic Intrauterine Hypoxia Alters Neurodevelopment in Fetal Sheep

摘要: Introduction: The presence of CHD in the fetus is associated with perturbations of brain growth and maturation, but the underlying mechanisms remain controversial. We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of CHD, would lead to abnormal neurodevelopment. Methods: Eight fetal sheep were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid filled environment under normoxic or hypoxic conditions. Total parenteral nutrition was provided. Age-matched control fetuses were harvested for comparison. At necropsy, brains were weighed and fixed for histopathology. Neurons were quantified in white matter (WM) tracts and the thickness of the external granular layer of the cerebellum was measured to assess neuronal migration. WM capillary density was quantified. Myelination was assessed using a WM integrity scale …