Effect of low and high doses of magnesium sulfate on the cerebro-vascular network

What is it about?

Cerebral palsy is the most prevalent cause of developing motor dysfunction affecting neonates. Clinical studies showed a beneficial effect of magnesium sulfate regarding the risk of cerebral palsy and its antenatal use is now recommended for neuroprotection by different colleges of obstetricians worldwide. However, regimen protocols fluctuate a lot and several clinical studies mentioned the possibility of adverse effects impacting the vascular system, keeping open the question of the optimal dosing.

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Why is it important?

The objectives were to perform a functional and mechanistic characterization of the effects of clinically relevant doses of magnesium sulfate on nervous and vascular systems by targeting neuroprotection, angiogenesis and hemodynamic factors and to compare on human fetuses the impact of a neuroprotective loading dose of magnesium sulfate on brain hemodynamic parameters. At a pre-clinical level, results showed that low and high neuroprotective doses of magnesium sulfate were equally potent to prevent cell oedema, cell burst, calcium mobilization and excitotoxic-induced necrosis. No side effects were found regarding caspase-3 activation and Bax expression. In contrast, magnesium sulfate exerted dose-dependent side-effects on brain angiogenesis, VEGF receptor and Hif-1 expression, endothelial viability and brain perfusion. At a clinical level, contrasting to higher loading doses, a 4 g bolus of magnesium sulfate did not alter fetal brain hemodynamic parameters. In conclusion, these data give the first mechanistic evidence of a double-sword and dose-dependent action of magnesium sulfate on nervous and vascular systems.

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