• Kendall M Lawrence, Patrick E McGovern, Ali Mejaddam, Avery C Rossidis, Heron Baumgarten, Aimee G Kim, Judith B Grinspan, Daniel J Licht, Enrico Radaelli, Jack Rychik, William H Peranteau, Marcus G Davey, Alan W Flake, and J William Gaynor.
• Department of Surgery, Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pa.
• J. Thorac. Cardiovasc. Surg. 2020 Jan 1; 159 (1): 270277270-277.

ObjectiveNeuroimmune cells, particularly microglia and astrocytes, play a critical role in neurodevelopment. Neurocognitive delays are common in children with congenital heart disease, but their etiology is poorly understood. Our objective was to determine whether prenatal hypoxemia, at levels common in congenital heart disease, induced neuroimmune activation to better understand the origins of neurobehavioral disorders in congenital heart disease.MethodsEight fetal sheep at gestational age 109 ± 3 days (term ∼145 days) were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 22 ± 2 days under normoxic (n = 4) or hypoxic (n = 4) conditions. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were stained with ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein antibodies to quantify microglia and astrocytes, respectively, in gray and white matter in frontotemporal and cerebellar sections. Microglia were classified into 4 morphologic types based on cell shape. Data were analyzed with 1-way analysis of variance or Fisher exact test, as appropriate.ResultsOxygen delivery was significantly reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min; P < .01). Rates of apoptosis were similar in hypoxic, normoxic, and intrauterine control animals in all examined areas. There were also no differences between groups in area occupied by glial fibrillary acidic protein-labeled astrocytes or ionized calcium-binding adaptor molecule 1-labeled microglia in all examined areas. However, round microglia were significantly increased in hypoxic animals compared with normoxic animals (33% vs 6%; P < .01) and control animals (33% vs 11%; P < .01).ConclusionsPrenatal hypoxemia altered microglial morphology without significant gliosis. Additional studies characterizing these mechanisms may provide insight into the origins of neurobehavioral disabilities in children with congenital heart disease.Copyright © 2019. Published by Elsevier Inc.

3 keywords...

hide…