Protective effect of MgSO4 infusion on NMDA receptor binding characteristics during cerebral cortical hypoxia in the newborn piglet

David J. Hoffman, Peter J. Marro, Jane E. McGowan, Om P. Mishra, Maria Delivoria-Papadopoulos

Research output: Contribution to journalArticle

Abstract

This study tests the hypothesis that magnesium, a selective non-competitive antagonist of the NMDA receptor, will attenuate hypoxia-induced alteration in NMDA receptors and preserve MK-801 binding characteristics during cerebral hypoxia in vivo. Anesthetized, ventilated and instrumented newborn piglets were divided into three groups: normoxic controls were compared to untreated hypoxic and Mg2+-treated hypoxic piglets. Cerebral hypoxia was induced by lowering the FiO2 to 5-7% and confirmed 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 hypoxia. Plasma Mg2+ concentrations increased from 1.6 ± 0.1 mg/dl to 17.7 ± 3.3 mg/dl. 3H-MK-801 binding was used as an index of NMDA receptor modification. The Bmax in control, hypoxic and Mg2+-treated hypoxic piglets was 1.09 ± 0.17, 0.70 ± 0.25 and 0.96 ± 0.14 pmoles/mg protein, respectively. The Kd for the same groups were 10.02 ± 2.04, 4.88 ± 1.43 and 8.71 ± 2.23 nM, respectively. The Bmax and Kd in the hypoxic group were significantly lower compared to the control 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, was lower in the hypoxic group compared to the control and Mg2+-treated hypoxic groups. These findings show that MgSO4 prevents the hypoxia-induced modification of the NMDA receptor and attenuates neuronal membrane dysfunction. We suggest that the administration of Mg2+ prior to and during hypoxia may be neuroprotective in vivo, possibly by reducing the NMDA receptor-mediated influx of calcium.

Original languageEnglish (US)
Pages (from-to)144-149
Number of pages6
JournalBrain Research
Volume644
Issue number1
DOIs
StatePublished - Apr 25 1994
Externally publishedYes

Keywords

  • Brain
  • Hypoxia
  • Magnesium
  • MK-801
  • Na, K-ATPase
  • NMDA receptor
  • Piglet

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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