Postischemic Intravenous Administration of Magnesium Sulfate Inhibits Hippocampal CA1 Neuronal Death after Transient Global Ischemia in Rats
| Autor: | Neville W. Knuckey, Bruno P. Meloni, Andrew N. Miles, Bernadette T. Majda |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell Survival
medicine.medical_treatment Ischemia Hippocampal formation Hippocampus Neuroprotection Loading dose Rats Sprague-Dawley Central nervous system disease Magnesium Sulfate Animals Medicine Infusions Intravenous Neurons Chemotherapy Dose-Response Relationship Drug business.industry Vascular disease medicine.disease Effective dose (pharmacology) Rats Neuroprotective Agents Ischemic Attack Transient Anesthesia Surgery Neurology (clinical) business |
| Zdroj: | Neurosurgery. 49:1443-1451 |
| ISSN: | 1524-4040 0148-396X |
| DOI: | 10.1097/00006123-200112000-00025 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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