Postischemic intravenous administration of magnesium sulfate inhibits hippocampal CA1 neuronal death after transient global ischemia in rats

Andrew N. Miles, Bernadette T. Majda, Bruno P. Meloni, Neville W. Knuckey, Christopher L. Taylor, Warren R. Selman, Ralph G. Dacey, R. Loch Macdonald, J. Max Findlay

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1443-1451
Number of pages9
JournalNeurosurgery
Volume49
Issue number6
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • CA1 neurons
  • Global cerebral ischemia
  • Magnesium
  • Magnesium chloride
  • Magnesium sulfate
  • Neuroprotection

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Postischemic intravenous administration of magnesium sulfate inhibits hippocampal CA1 neuronal death after transient global ischemia in rats'. Together they form a unique fingerprint.

  • Cite this

    Miles, A. N., Majda, B. T., Meloni, B. P., Knuckey, N. W., Taylor, C. L., Selman, W. R., Dacey, R. G., Macdonald, R. L., & Findlay, J. M. (2001). Postischemic intravenous administration of magnesium sulfate inhibits hippocampal CA1 neuronal death after transient global ischemia in rats. Neurosurgery, 49(6), 1443-1451. https://doi.org/10.1097/00006123-200112000-00025