The effects of systemic magnesium sulfate infusion on brain magnesium concentrations and energy state during hypoxia-ischemia in newborn miniswine.
Academic Article
Overview
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.
