Fetal rat brain injury due to severe maternal hypoxia: prevention by magnesium sulfate

M. Hallak, J. W. Hotra, W. J. Kupsky

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OBJECTIVE: To determine whether severe maternal hypoxia during the third trimester of pregnancy may cause neuronal damage in fetal rat brain, and whether magnesium sulfate (MgSO4) may prevent this effect. STUDY DESIGN: Four groups of pregnant rats (n = 21) were studied at 17 gestational days. Group #1: Saline injected and room air (RA, n = 6); Group #2: MgSO4 injected and room air (n = 5); Group #3: Saline injected and hypoxia chamber (n = 5); Group #4: MgSO4 injected and hypoxia chamber (n = 5}. Subcutaneous maternal MgSO4 injection protocol included loading dose of 270 mg/kg followed by 27 mg/kg even7 20 minutes for 4 hours. Saline rats were injected with the same volume and schedule. Hypoxia chamber protocol included a gas mixture of 9% oxygen, 3% CO2, and nitrogen for 2 hours. After 72 hours of recovery, at 20 days' gestation fetal cardiovascular systems were perfused with 10% formalin. Brains were obtained and embedded in paraffin, sectioned in corona) plane, and stained \\ith hemaloxvlin & eosin. Histologie grading was performed by a trained neuropathologist blinded to the protocol. Ten brain regions have been examined bilaterally, including: Cortex {frontal and parietal lobes, entorhinal), white matter (frontal and parietal lobes). Hippocampus (pyramidalis, dentate gyrus), basal ganglia, thalamus, and hypothalamus. RESULTS: Exposure to the gas mixture resulted in decreased maternal p(>._, and pH (p < 0.0001). No significant change in maternal pCO<2 status have been noted. Exposure to ihe MgSO, injection protocol resulted in increased blood magnesium level from 1.52 ±0.2 to 3.77 ±0.7 {p < 0.0001). Fetal Brain Region Saline & RA MgSO4 & RA Saline & Hypoxia MgSO4 & Hypoxia Hippo-pyr. 0/22(0%) 5/21 (24%) 8/21 (38%)* 4/25(17%) Thalamus 0/19 (0%.} 1 -'20 (5%) 7/18 (39%)* 1/24 (4%) *p < 0.05 CONCLUSION: Severe maternal hypoxia resulted in significant increasein isolaied fetal neuronal damage, including necrosis and shrinkage of cells, with increased karyorrhexis (fragmeutaiion and breakage of the nucleus) in the hippocampus (pyramidalis), and thalamus compared to controls. This effect was significantly reduced b\ peripheral maternal MgSO4 administration.

Original languageEnglish
Pages (from-to)S167
JournalActa Diabetologica Latina
Issue number1 PART II
StatePublished - 1 Dec 1997
Externally publishedYes


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