Comparison of the efficacy of mild hypothermia (35°c) and moderate hypothermia (33°c), alone or combined with magnesium treatment, when commenced 2 or 4 hours after global cerebral ischemia in rats.
We first assessed the neuroprotective efficacy of mild hypothermia (35°C/24 hours) alone and in combination with magnesium (intravenous loading dose: 360 μmol/kg; 48 hours infusion: 120 μmol/kg/h) commencing 4 hours after global ischemia. Treatment with mild hypothermia alone (CA1 survival rate: 8.7%±0.9%) or with magnesium (9.0%±2.9%) did not significantly increase hippocampal CA1 neuronal survival compared with saline-treated controls (7.1%±0.7%). Next, we assessed mild hypothermia (35°C/24 hours) and moderate hypothermia (33°C/24 hours), alone or in combination with magnesium, when commenced 2 hours after global ischemia. At this time point, all treatments significantly increased CA1 neuronal survival compared with saline controls (CA1 survival rates: mild hypothermia: 13.6%±1.8%; mild hypothermia + magnesium: 19.4%±8.7%; moderate hypothermia: 15.9%±4.1%; moderate hypothermia + magnesium: 21.1%±11.2%; saline control: 6.7%±1.6%; p<0.001). Although a trend for increased neuroprotection was observed when hypothermia was combined with magnesium, it did not reach statistical significance. It also appears that when a 24-hour hypothermia treatment is commenced earlier (≤2 hours postischemia) there is no difference in efficacy between mild and moderate hypothermia.
1 Centre for Neuromuscular and Neurological Disorders, University of Western Australia , Australian Neuromuscular Research Institute, Department of Neurosurgery, Sir Charles Gairdner Hospital, Western Australia, Australia .
Li-Xian
LX
Li
Kym
K
Campbell
Shiguang
S
Zhao
Neville W
NW
Knuckey
Bruno P
BP
Meloni