The Effect of MgSO₄ Treatment Post In Utero Hypoxia on Cerebral Cortical Nuclear Membranes in the Term Guinea Pig Fetus

Abstract 1232 Poster Session II, Sunday, 5/2 (poster 69)

The present study tests the hypothesis that MgSO₄ administration post in utero hypoxia will attenuate hypoxia-induced alterations of neuronal cellular and nuclear membranes in the fetal guinea pig brain. Fifteen pregnant guinea pigs at term were studied: 5 normoxic (Nx), 5 hypoxic (Hx) and 5 post-hypoxia Mg-treated (post-HxMg). Hypoxia was induced by exposure to a FiO₂ of 8% for 1 hr; following hypoxia the treated group received a 300mg/kg bolus dose of MgSO₄ and then 100mg/kg/hr for 4 hr. Fetal brain tissue was obtained following 24 hr of in utero recovery in all groups. Cerebral hypoxia was documented biochemically by measuring tissue levels of ATP and phosphocreatine. The activity of Na⁺,K⁺ -ATPase was determined as an index of cell membrane function while products of lipids peroxidation (fluorescent compounds and conjugated dienes) were measured as an index of nuclear membrane alteration. ATP and PCr levels (µmoles/g brains) were 0.88 ± 0.35 and 0.68 ± 0.35 in Hx, significantly lower than Nx 4.95 ± 0.70 and 4.50 ± 0.40 (p<0.05 for both) while in post-HxMg values were 2.98 ± 0.54 and 2.30 ± 0.41, lower than Nx but significantly higher than in Hx. Na⁺,K⁺-ATPase activity significantly decreased in Hx (32.5 ± 1.9 µmoles Pi/mg protein/hr vs 44.4 ± 5.1 in Nx, p<0.05), whereas in post-HxMg the enzyme activity was significantly higher as compared to the hypoxic group (post-HxMg 39.0 ± 5.3 vs Hx 32.4 ± 1.9, p<0.05) and not different from the normoxic group. Nuclear membrane fluorescent compounds increased in the hypoxic group as compared to the normoxic animals (Hx 17.8 ± 2.3, Nx 9.3 ± 0.6 µg quinine sulfate/g brain, p<0.05). However, the levels in post-HxMg (12.8 ± 2.7) were not different from the Nx (9.3 ± 0.6, p<0.05). Conjugated dienes increased significantly in both the hypoxic and Mg-treated hypoxic groups as compared to the normoxic (Hx 2.2 ± 1.7, post-HxMg 2.0 ± 1.9µmoles/g brain, p<0.05 vs Nx of 0). Thus MgSO₄ administration following in utero hypoxia attenuated hypoxia-induced alterations in both the neuronal cellular and nuclear membranes at 24 hrs after the hypoxic insult. We speculate that blockade of the NMDA receptor by Mg⁺⁺ prevents the hypoxia-induced NMDA receptor-mediated increase in intracellular Ca⁺⁺, thereby decreasing oxygen free radical-induced changes in membrane structure and function.

(Funded by WUH/OBR-98 and NIH-HD-20337)