Magnesium Sulfate Protection of Fetal Rat Brain From Severe Maternal Hypoxia

Abstract

In Brief Objective To determine whether severe maternal hypoxia affects fetal rat physical characteristics and causes neuronal damage, and whether magnesium sulfate can decrease these effects. Methods At 17 days gestation, rats were randomly assigned to one of four groups that received saline injections and room air (n = 6), magnesium sulfate and room air (n = 5), saline and hypoxia (n = 5) or magnesium sulfate and hypoxia (n = 5). Maternal magnesium sulfate or saline injections were given for 4 hours. In groups 3 and 4 this was followed by a hypoxia chamber protocol that included a gas mixture of 9% oxygen and 3% carbon dioxide for 2 hours. After 72 hours of recovery, fetuses were delivered abdominally, perfused transcardially, and brains removed intact. Fetal body and brain weight and size were measured. Brains were embedded in paraffin, sectioned, and stained. A neuropathologist masked to the protocol performed histologic grading of brain regions. Results Exposure to the hypoxia chamber resulted in decreased maternal oxygen tension and pH (from 82.8 ± 20.0 to 49.2 ± 14.4 mmHg, and from 7.37 ± 0.05 to 7.20 ± 0.04, respectively; P < .005). Magnesium sulfate administration resulted in higher magnesium levels in blood (from 1.52 ± 0.2 to 3.77 ± 0.7 mg/dL; P < .001). The hypoxia protocol resulted in a significant decrease in fetal body and brain size, but not weight. Hypoxia also caused an increase in the proportion of fetal rats that had brain injury, including shrinkage of cells and karyorrhexis in the hippocampus and thalamus (from 0% to 38.1% and 38.9%, respectively; P < .05). Magnesium sulfate reduced these effects on fetal brain histopathology and size. Conclusion Severe maternal rat hypoxia resulted in significant fetal neuronal damage and decreased fetal body and brain size. Maternal magnesium sulfate administration reduced the effect of hypoxia on fetal brain histopathology and size without affecting body size. Subcutaneous maternal magnesium sulfate administration protected against fetal neuronal damage caused by subsequent maternal hypoxia.