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. CONCLUSION: 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).