Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia.
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.


CONCLUSIONS
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.
Hallak
M
M
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. mhallak@bgumail.bgu.ac.il
Hotra
J W
JW
Kupsky
W J
WJ
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control*; D005333:Fetus / Q000473:pathology; D000860:Hypoxia / Q000188:drug therapy*; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans
D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate