Neuroprotective activity with
magnesium associated with animal models of cerebral ischaemia, seizure, perinatal
hypoxia/ischaemia, subarachnoid haemorrhage and
traumatic brain injury has provided the justification for clinical
stroke trials. However, the recent IMAGES
stroke clinical trial found
magnesium to be largely ineffective. Hence, due to the negative
stroke trial outcome, current FAST-MAG trial and our own experience with
magnesium in cerebral ischaemia animal models, we thought it prudent to review these preclinical and clinical studies. We reviewed nine studies describing the use of
magnesium following global cerebral ischaemia and fourteen following focal cerebral ischaemia. Four global ischaemia and six focal ischaemia studies did not show a significant
neuroprotective effect with
magnesium. In the majority of positive
magnesium studies animal body temperature was not monitored post-ischaemia. Thus the effects of post-ischaemic
hypothermia cannot be ruled out as a confounding factor in positive
magnesium cerebral ischaemia studies. Moreover, data from our own laboratory indicates that
magnesium is only neuroprotective when combined with post-ischaemic
hypothermia. These data provide a possible explanation of why the IMAGES trial was largely unsuccessful, as current
stroke patient management does not involve
hypothermia induction. Future preclinical and clinical cerebral ischaemia trials with
magnesium should consider combining treatment with mild
hypothermia.