Kym Campbell1, Bruno P Meloni, Neville W Knuckey. 1. Centre for Neuromuscular and Neurological Disorders/University of Western Australia, Australian Neuromuscular Research Institute, Department of Neurosurgery/Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
Abstract
BACKGROUND AND PURPOSE: Using transient focal and global cerebral ischemia models in the rat, we have previously shown that MgSO4 is not neuroprotective unless it is combined with mild hypothermia. This study establishes a therapeutic time window for combined MgSO4 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 MgSO4 infusion (360 micromol/kg, then 120 micromol/kg/h) and mild hypothermia (35 degrees C) or with vehicle for 24 h. At the 2 h time point, treatment with hypothermia alone and MgSO4 alone were also assessed. Infarct volumes were measured 48 h after MCAO induction. RESULTS: After permanent MCAO, combined MgSO4 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 MgSO4 alone groups. CONCLUSIONS: These findings support our earlier work highlighting the neuroprotective effect of MgSO4 when combined with mild hypothermia, even when treatment is delayed by several hours.
BACKGROUND AND PURPOSE: Using transient focal and global cerebral ischemia models in the rat, we have previously shown that MgSO4 is not neuroprotective unless it is combined with mild hypothermia. This study establishes a therapeutic time window for combined MgSO4 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 MgSO4 infusion (360 micromol/kg, then 120 micromol/kg/h) and mild hypothermia (35 degrees C) or with vehicle for 24 h. At the 2 h time point, treatment with hypothermia alone and MgSO4 alone were also assessed. Infarct volumes were measured 48 h after MCAO induction. RESULTS: After permanent MCAO, combined MgSO4 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 MgSO4 alone groups. CONCLUSIONS: These findings support our earlier work highlighting the neuroprotective effect of MgSO4 when combined with mild hypothermia, even when treatment is delayed by several hours.
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Authors: William R Gow; Kym Campbell; Amanda J Meade; Paul M Watt; Nadia Milech; Neville W Knuckey; Bruno P Meloni Journal: J Cereb Blood Flow Metab Date: 2011-10-05 Impact factor: 6.200