461 Magnesium sulphate (Mg) doses for neuroprotection: low is better

Abstract

Antenatal magnesium sulphate (Mg) is recommended for neuroprotection associated with preterm birth. However, the exact dose and duration, are still under debate. The ACOG recommends to use one of three protocols with a total Mg supplementation of 4 (loading only) to 31.5grams (loading+maintenance). Recent studies imply that while low dose Mg may help neuronal survival, higher doses may promote cell apoptosis. In clinical trials preterm neonates with high MG had increase morbidity and mortality. In the present study we sought to investigate the optimal dosing of Mg in a preterm rat model. Pregnant rats at 20d of gestation (30 total, N = 5) received i.p. LPS (500 μg/kg) or saline. Dams were randomized to s.c. saline, Low Mg-loading dose of 150mg/kg and High Mg-loading dose (150 mg/kg) +maintenance (15mg/kg q20 min for 2h prior to and following the i.p. injections). Dams were sacrificed 4h following the first injection. Fetal brains were analyzed for inflammatory cytokines (western blot). Maternal and fetal serum Mg levels and inflammatory cytokines were analyzed and compared between groups (ELISA). Maternal and fetal serum Mg levels were lowest in the SAL groups, increased in Low Mg group and were highest in the High Mg groups. Fetal brain IL-6 and TNF-α protein levels increased in the LPS/SAL compared to SAL/SAL groups (IL-6 2.06+0.05 VS 0.75+0.12U, TNF-α 2.11+0.04 vs 0.76+0.12U). Maternal Mg administration reduced fetal brain inflammatory cytokines following LPS compared to LPS/SAL group to basal levels (IL-6 0.71+0.04 vs 2.06+0.05 U, TNF-α 0.75+0.13U) for LPS/Low Mg and (IL-6 0.73±0.26 VS 2.06+0.05U, TNF-α 0.74+0.33 vs 2.11+0.04U for LPS/High Mg respectively, p<0.05). Similar pattern was demonstrated in maternal and fetal serum. Fetal serum Mg levels increase in direct proportion to maternal Mg dose. Low Mg was as effective as High Mg in reducing inflammatory markers. Our results imply that loading dose regime is effective in preventing neuroinflammation and may prevent long term sequela potentially associated with high fetal Mg levels.View Large Image Figure ViewerDownload Hi-res image Download (PPT)