Combined magnesium and mild hypothermia (35 °C) treatment reduces infarct volumes after permanent middle cerebral artery occlusion in the rat at 2 and 4, but not 6 h

Abstract

Background and purpose Using transient focal and global cerebral ischemia models in the rat, we have previously shown that MgSO 4 is not neuroprotective unless it is combined with mild hypothermia. This study establishes a therapeutic time window for combined MgSO 4 and mild hypothermia treatment after permanent middle cerebral artery occlusion (MCAO). Methods Rats were subjected to permanent intraluminal thread MCAO and animals were treated 2, 4 or 6 h after ischemia with a MgSO 4 infusion (360 μmol/kg, then 120 μmol/kg/h) and mild hypothermia (35 °C) or with vehicle for 24 h. At the 2 h time point, treatment with hypothermia alone and MgSO 4 alone were also assessed. Infarct volumes were measured 48 h after MCAO induction. Results After permanent MCAO, combined MgSO 4 and hypothermia treatment reduced infarct volumes by 54% at 2 h ( P = 0.048) and by 39% at 4 h ( P = 0.012), but there was no treatment effect detected at 6 h or in the hypothermia alone or MgSO 4 alone groups. Conclusions These findings support our earlier work highlighting the neuroprotective effect of MgSO 4 when combined with mild hypothermia, even when treatment is delayed by several hours.