Post-ischemic modest hypothermia (35°C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats

Abstract

In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35°C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 μmol/kg MgSO 4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 μmol/kg/h. Immediately post-ischemia, body temperature was lowered to 35°C for 6 h or maintained at 37°C. In experimental group 2, 2 h after ischemia, rats received the MgSO 4 LD/IVI and/or had their body temperature lowered to 35°C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9% neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.