Efficacy of mild hypothermia (35 °C) and moderate hypothermia (33 °C) with and without magnesium when administered 30 min post-reperfusion after 90 min of middle cerebral artery occlusion in Spontaneously Hypertensive rats

Abstract

In this study we compared the efficacy of mild (35°C) and moderate (33°C) hypothermia alone and when combined with magnesium in a transient focal cerebral ischaemia rat model. Spontaneously Hypertensive rats were subjected to 90min of transient intraluminal thread middle cerebral artery occlusion (MCAO). Thirty minutes after reperfusion animals were treated with mild (35°C/24h) or moderate (33°C/24h) hypothermia combined with either magnesium (intravenous MgSO4 infusion: 360μmol/kg, then 120μmol/kg/h for 24h) or a similar volume of saline. Control animals were maintained normothermic (37°C/24h) and received vehicle infusion (saline for 24h). Infarct volumes and functional assessment (bi-symmetrical adhesive tape removal) were measured 48h after MCAO induction. After transient MCAO, only moderate hypothermia and mild hypothermia combined with magnesium treatment significantly reduced infarct volumes by 32.9% (P=0.01) and by 24.8% (P=0.046), respectively. Mild hypothermia alone reduced infarct volume by 23.8%, but did not reach statistical significance (P=0.054), while moderate hypothermia combined with magnesium reduced infarct volume by 17.3% (P=0.17). No treatment improved adhesive tape removal time. In summary, moderate hypothermia and mild hypothermia with or without magnesium can reduce infarct volume, however magnesium may reduce the efficacy of moderate hypothermia. Given the potential advantages of mild hypothermia over moderate hypothermia in terms of side-effects and induction, and the potential beneficial effects of magnesium, these findings have important implications for the use of hypothermia for stroke.