Magnesium and neuroprotection in stroke

Abstract

Magnesium, an important cation for normal brain tissue function, has specific cellular actions that are likely to counteract damaging ischaemic processes. In 1991, magnesium was first trialled experimentally as a neuroprotective agent in a rat stroke model with positive results. Subsequently, several other magnesium studies using animal stroke models have reported positive outcomes, though others have not shown a neuroprotective effect. In 2004, the large scale Intravenous Magnesium Efficacy in Stroke (IMAGES) clinical trial found magnesium to be largely ineffective in treating strokes, though subsequent analysis revealed a small but significant benefit in lacunar stroke patients. In this review, we present the findings of published animal and human stroke studies (focal cerebral ischaemia) that have used magnesium as a neuroprotective therapy, and discuss the possible reasons for the somewhat inconsistent results. Our interpretation of the data suggests that, in many experimental studies, post-ischaemic hypothermia has probably been a confounding factor in those with positive outcomes. In addition, experimental design has varied widely with respect to magnesium dosage, and to the time and route of magnesium administration. Importantly, data from our own laboratory using experimental stroke models indicates that magnesium is only neuroprotective when combined with post-ischaemic hypothermia. Finally, the FAST-Mag trial, following on from the IMAGES trial, will soon be complete, and it is anticipated that the outcome of this trial will provide a more definitive answer as to whether magnesium is neuroprotective following stroke.