Abstract
The mechanism of neuroprotection associated with systemically administered magnesium remains unclear. This investigation examined the acute effects of systemically administered MgSO4 on brain extracellular ([Mg]ecf) and intracellular ([Mg]i) fluid Mg concentrations, specific brain phosphorylated metabolites, and brain intracellular pH. Miniswine were studied with P-31 magnetic resonance spectra, to derive [Mg]i, and brain microdialysis probes, to measure [Mg]ecf. Animals were infused with MgSO4 (n = 5, 275 mg/kg over 30 min followed by 100 mg/kg over 30 min, designated MgHI) or Na2SO4 (n = 5, designated NaHI), and both groups underwent hypoxia-ischemia (HI) over the last 15 min of the infusions. Groups differed in plasma [Mg] at the completion of HI (9.1 ± 1.5 versus 1.1 ± 0.6 mM for MgHI and NaHI, respectively, p < 0.05). MgHI had elevations of [Mg]ecf (0.23 ± 0.11 and 0.40 ± 0.14 mM at control and completion of HI, respectively), and [Mg]ecf was unchanged for NaHI (p < 0.05 versus MgHI). At the completion of HI, MgHI had greater decreases in nucleoside triphosphate (NTP) (48 ± 6% of control), and more brain acidosis after HI (6.01 ± 0.07) compared with NaHI (NTP, 70 ± 3% of control; brain pH, 6.51 ± 0.14, both p < 0.05 versus MgHI). [Mg]i increased to elevated values during HI in both MgHI and NaHI (p < 0.05 versus control of each group) and remained higher in MgHI over the next 25 min (p < 0.05 versus NaHI). There were inverse correlations during HI between [Mg]i and brain NTP (r2 = 0.73 and 0.59 for MgHI and NaHI, respectively), and brain acidosis (r2 = 0.85 and 0.85 for MgHI and NaHI, respectively) in each group. These findings indicate complex effects of Mg on the brain. Elevation of [Mg]ecf may be beneficial with regards to excitatory neurotransmitters. However, greater disturbance of brain NTP concentration, more acidosis, and the increase in [Mg]i may offset any benefit. The results warrant further investigation using indicators of neuronal injury to determine whether Mg supplementation provides neuroprotection.
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Abbreviations
- HI:
-
hypoxia-ischemia
- HR:
-
heart rate
- MAP:
-
mean arterial pressure
- [Mg]plasma:
-
plasma Mg concentration
- [Mg]ecf:
-
extracellular fluid Mg concentration
- [Mg]i:
-
intracellular fluid Mg concentration
- NTP:
-
nucleoside triphosphate
- 31P NMR:
-
phosphorus 31 nuclear magnetic resonance
- PCr:
-
phosphocreatine
- pHi:
-
intracellular pH
- Pi:
-
inorganic phosphate
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Acknowledgements
The authors thank William Gitomer, Ph.D., and the staff of the Mineral and Metabolism Laboratory at Parkland Hospital, Dallas, TX.
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Supported, in part, by a grant from the Wyeth Pediatrics Neonatology Research Fund.
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Gee, J., Corbett, R., Perlman, J. et al. The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine. Pediatr Res 55, 93–100 (2004). https://doi.org/10.1203/01.PDR.0000099771.39629.E5
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DOI: https://doi.org/10.1203/01.PDR.0000099771.39629.E5
