Fetal Neuroprotective Mechanism of Maternal Magnesium Sulfate: Proteomic Analysis

Abstract

Mg supplementation has been shown to protect preterm fetuses from white and gray matter damage, but the mechanism is unclear. The purpose of this study was to study the effect of maternal inflammation on the overall protein panel of the fetal rat brain, as well as the neuroprotective effect of magnesium-sulfate (MG). Pregnant rats at e20 (n = 6, 18 total) received injections of i.p. lipopolysaccharide (LPS) 500 ug/kg or control saline (SAL) at time 0. Dams were randomized to treatment with s.c. MG (270 mg/kg loading followed by 27 mg/kg q20 min) or saline (SAL) from -2 to +2 h, followed by an additional injection of MG (270 mg/kg) at +2 h. At 4 h after LPS administration, fetal brains were collected from the 3 treatment groups (LPS/SAL, LPS/MG, SAL/SAL) and analyzed by proteomic technique. LPS significantly decreased fetal brain complement C3, alpha-1-antiproteinase, metallothionein-3, alpha-2-macroglobulin, neurosecretory protein VGF, glutathione S-transferase mu 2, fam91a1, cnot7, mitogen-activated protein kinase levels, and significantly increased fetal brain Hbg1, while MG treatment normalized these measures to normal values. Maternal inflammation may cause brain injury via pathways other than the activation of neurotoxic cytokines; this effect could be due to increased/decreased production of certain proteins associated with securing oligodendrocytes, encouraging neuronal growth in the brain, or protecting against cerebral ischemia. MG's neuroprotective activity may be achieved by modifying the effect of LPS on proteins involved in early brain development.

Keywords: Asphyxia; Infection; Magnesium sulfate; Neuroprotection; Preterm.