In this study, we investigated the efficacy of pre- and 2 h post-ischemic
magnesium treatment with different durations of modest
hypothermia (35 degrees 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 micromol/kg MgSO4 immediately before
ischemia followed by a 48 h
intravenous infusion (IVI) at 120 micromol/kg/h. Immediately post-
ischemia, body temperature was lowered to 35 degrees C for 6 h or maintained at 37 degrees C. In experimental group 2, 2 h after
ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35 degrees 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.