Post-ischemic modest hypothermia (35°C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats

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    Abstract

    In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35°C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 μmol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 μmol/kg/h. Immediately post-ischemia, body temperature was lowered to 35°C for 6 h or maintained at 37°C. In experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35°C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9% neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.
    Original languageEnglish
    Pages (from-to)361-368
    JournalExperimental Neurology
    Volume193
    Issue number2
    DOIs
    Publication statusPublished - 2005

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    Hypothermia
    Brain Ischemia
    Magnesium
    Ischemia
    Body Temperature
    Intravenous Infusions
    Therapeutics
    Induced Hypothermia

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    @article{7af68329ab4c4f7487cc107d05364f65,
    title = "Post-ischemic modest hypothermia (35°C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats",
    abstract = "In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35°C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 μmol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 μmol/kg/h. Immediately post-ischemia, body temperature was lowered to 35°C for 6 h or maintained at 37°C. In experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35°C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4{\%} CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1{\%} and 37.9{\%} neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43{\%} CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76{\%} neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.",
    author = "H. Zhu and Bruno Meloni and Christina Bojarski and M.W. Knuckey and Neville Knuckey",
    year = "2005",
    doi = "10.1016/j.expneurol.2005.01.022",
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    AU - Meloni, Bruno

    AU - Bojarski, Christina

    AU - Knuckey, M.W.

    AU - Knuckey, Neville

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    N2 - In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35°C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 μmol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 μmol/kg/h. Immediately post-ischemia, body temperature was lowered to 35°C for 6 h or maintained at 37°C. In experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35°C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9% neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.

    AB - In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35°C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 μmol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 μmol/kg/h. Immediately post-ischemia, body temperature was lowered to 35°C for 6 h or maintained at 37°C. In experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35°C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9% neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.

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