Postischemic intravenous administration of magnesium sulfate inhibits hippocampal CA1 neuronal death after transient global ischemia in rats.
OBJECTIVE
We aimed to determine an effective dose schedule for intravenously administered magnesium, to establish its neuroprotective efficacy in both pre- and postischemic treatment paradigms, and to compare the neuroprotective properties of MgSO(4) and MgCl(2).


METHODS
Rats that had been subjected to the bilateral carotid artery occlusion plus hypotension model of transient forebrain cerebral ischemia received either an intravenously administered loading dose (LD) of 360 micromol/kg MgSO(4) only or an intravenously administered LD of 360 micromol/kg followed by a 48-hour intravenous infusion of MgSO(4) at either 60, 120, 240, or 480 micromol/kg/h. For evaluation of the efficacy of MgSO(4) after ischemia, the dose (LD, 360 micromol/kg; infusion, 120 micromol/kg/h) that provided maximal neuroprotection before ischemia was administered 4, 8, 12, or 24 hours after ischemia. MgCl(2) (LD, 360 micromol/kg; infusion, 120 micromol/kg/h) was administered before and 8 hours after ischemia. At 7 days after ischemia, hippocampal CA1 neurons were histologically examined for protection.


RESULTS
Animals that received the LD only demonstrated 33% hippocampal CA1 neuronal survival. Animals that received the LD followed by continuous infusion of MgSO(4) at either 60, 120, 240, or 480 micromol/kg/h demonstrated 30, 80, 16, and less than 5% CA1 neuronal survival, respectively. MgSO(4) treatment commencing at 4, 8, 12, or 24 hours resulted in 82, 71, 52, and 33% CA1 neuronal survival, respectively. Preischemic and 8-hour postischemic administration of MgCl(2) resulted in 50% and less than 5% CA1 neuronal survival, respectively.


CONCLUSIONS
These results demonstrate a neuroprotective intravenous dose of MgSO(4), which is effective when administered before or late after ischemia, and a previously uncharacterized dose-response curve for MgSO(4).
Miles
A N
AN
Department of Neurosurgery, Sir Charles Gairdner Hospital, Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Australia.
Majda
B T
BT
Meloni
B P
BP
Knuckey
N W
NW
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate