PROTECTIVE EFFECT OF MGSO4 INFUSION ON NMDA RECEPTOR-BINDING CHARACTERISTICS DURING CEREBRAL CORTICAL HYPOXIA IN THE NEWBORN PIGLET

This study tests the hypothesis that magnesium, a selective non-compet itive antagonist of the NMDA receptor, will attenuate hypoxia-induced alteration in NMDA receptors and preserve MK-801 binding characteristi cs during cerebral hypoxia in vivo. Anesthetized, ventilated and instr umented newborn piglets were divided into three groups: normoxic contr ols were compared to untreated hypoxic and Mg2+-treated hypoxic piglet s. Cerebral hypoxia was induced by lowering the FiO(2), to 5-7% and co nfirmed biochemically by a decrease in the levels of phosphocreatine ( 82% lower than control). The Mg2+-treated group received MgSO4 600 mg/ kg over 30 min followed by 300 mg/kg administered during 60 min of hyp oxia. Plasma Mg2+ concentrations increased from 1.6 +/- 0.1 mg/dl to 1 7.7 +/- 3.3 mg/dl. H-3-MK-801 binding was used as an index of NMDA rec eptor modification. The B-max in control, hypoxic and Mg2+-treated hyp oxic piglets was 1.09 +/- 0.17, 0.70 +/- 0.25 and 0.96 +/- 0.14 pmoles /mg protein, respectively. The K-d for the same groups were 10.02 +/- 2.04, 4.88 +/- 1.43 and 8.71 +/- 2.23 nM, respectively. The B-max and K-d in the hypoxic group were significantly lower compared to the cont rol and Mg2+-treated hypoxic groups, indicating a preservation of NMDA receptor number and affinity for MK-801 during hypoxia with Mg2+ The activity of Na+, K+ ATPase, a marker of neuronal membrane function, wa s lower in the hypoxic group compared to the control and Mg2+-treated hypoxic groups. These findings show that MgSO4 prevents the hypoxia-in duced modification of the NMDA receptor and attenuates neuronal membra ne dysfunction. We suggest that the administration of Mg2+ prior to an d during hypoxia may be neuroprotective in vivo, possibly by reducing the NMDA receptor-mediated influx of calcium.