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 adminstered magnesium, to establish its neuroprotective efficacy in both pre- and postischemic treatment paradigms, and to compare the neuroprotective properties of MgSO₄ and MgCl₂. 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 μmol/kg MgSO₄ only or an intravenously administered LD of 360 μmol/kg followed by a 48-hour intravenous infusion of MgSO₄ at either 60, 120, 240, or 480 μmol/kg/h. For evaluation of the efficacy of MgSO₄ after ischemia, the dose (LD, 360 μmol/kg; infusion, 120 μmol/kg/h) that provided maximal neuroprotection before ischemia was administered 4, 8, 12, or 24 hours after ischemia. MgCl₂ (LD, 360 μmol/kg; infusion, 120 μmol/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 MgSO₄ at either 60, 120, 240, or 480 μmol/kg/h demonstrated 30, 80, 16, and less than 5% CA1 neuronal survival, respectively. MgSO₄ 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 MgCl₂ resulted in 50% and less than 5% CA1 neuronal survival, respectively. CONCLUSION: These results demonstrate a neuroprotective intravenous dose of MgSO₄, which is effective when administered before or late after ischemia, and a previously uncharacterized dose-response curve for MgSO₄.