title: Intravenous administration of magnesium is only neuroprotective following transient global ischemia when present with post-ischemic mild hypothermia.
abstract: We hypothesized that post-ischemic hypothermia plays an important role in magnesium mediated neuroprotection following global cerebral ischemia. To test this hypothesis, we subjected rats to 8 min of global cerebral ischemia and magnesium treatment with and without post-ischemic body temperature maintenance. In Group 1, rats received an intravenously administered loading dose (LD) of 360 micromol/kg MgSO4 immediately before ischemia followed by a 48-h intravenous infusion (IVI) at either 60, 120 or 240 micromol/kg/h. Animal body temperature was kept at 37+/-0.2 degrees C during ischemia and between 36.6 and 37.8 degrees C for 6 h after ischemia. In Group 2, rats received a 360 micromol/kg MgSO4 LD followed by a 48-h IVI of either 120 or 240 micromol/kg/h MgSO4. In this group, body temperature following ischemia was monitored but not regulated. Control animals in Groups 1 and 2 received normal saline. Seven days after ischemia, hippocampal CA1 neurons were histologically examined. All Group 1 MgSO4-treated and control animals demonstrated less than 6% hippocampal CA1 neuronal survival. In Group 2, the rectal temperature of MgSO4-treated and control animals spontaneously dropped as low as 35.4 degrees C during the 6-h post-ischemia monitoring period. In addition, Group 2 animals that received the LD followed by an IVI of 120 or 240 micromol/kg/h MgSO4 demonstrated 34% (p<0.05) and 20% (p=0.936) CA1 neuronal survival, respectively. The CA1 neuronal survival in saline-treated control animals in both groups was less than 6%. Our data demonstrate only the combination of MgSO4 treatment and post-ischemic mild hypothermia is neuroprotective following global ischemia.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute, Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Zhu
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Moore
authors.forename: Bernadette T
authors.initials: BT
authors.lastname: Majda
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
mesh_terms: D000818:Animals; D007035:Hypothermia / Q000175:diagnosis / Q000209:etiology*; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D008274:Magnesium / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D008274:Magnesium