Magnesium sulfate therapy during asphyxia in near-term fetal lambs does not compromise the fetus but does not reduce cerebral injury

Haan, Harmen H. de; Gunn, Alistair J.; Williams, Chris; Heymann, Michaël; Gluckman, Peter D.

doi:10.1016/s0002-9378(97)80005-1

Cited by 88 publications

(39 citation statements)

References 24 publications

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“…In contrast, systemic magnesium administration after HI in newborn piglets did not prevent the development of delayed energy failure, but much lower [Mg] plasma were achieved compared with the present study (44). Furthermore, systemic magnesium administration after asphyxia in fetal sheep did not reduce the extent of cytotoxic edema, did not improve the recovery of the EEG, and did not alter the histologic outcome (45). Retrospective epidemiologic human data, however, suggests that in utero exposure of the fetus to magnesium is associated with less cerebral palsy in children of very low birth weight (46,47).…”

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confidence: 86%

The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine

et al. 2004

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The mechanism of neuroprotection associated with systemically administered magnesium remains unclear. This investigation examined the acute effects of systemically administered MgSO 4 on brain extracellular ([Mg] ecf ) and intracellular ([Mg] i ) fluid Mg concentrations, specific brain phosphorylated metabolites, and brain intracellular pH. Miniswine were studied with P-31 magnetic resonance spectra, to derive [Mg] i , and brain microdialysis probes, to measure [Mg] ecf . Animals were infused with MgSO 4 (n ϭ 5, 275 mg/kg over 30 min followed by 100 mg/kg over 30 min, designated MgHI) or Na 2 SO 4 (n ϭ 5, designated NaHI), and both groups underwent hypoxia-ischemia (HI) over the last 15 min of the infusions. Groups differed in plasma [Mg] at the completion of HI (9.1 Ϯ 1.5 versus 1.1 Ϯ 0.6 mM for MgHI and NaHI, respectively, p Ͻ 0.05). MgHI had elevations of [Mg] ecf (0.23 Ϯ 0.11 and 0.40 Ϯ 0.14 mM at control and completion of HI, respectively), and [Mg] ecf was unchanged for NaHI (p Ͻ 0.05 versus MgHI). At the completion of HI, MgHI had greater decreases in nucleoside triphosphate (NTP) (48 Ϯ 6% of control), and more brain acidosis after HI (6.01 Ϯ 0.07) compared with NaHI (NTP, 70 Ϯ 3% of control; brain pH, 6.51 Ϯ 0.14, both p Ͻ 0.05 versus MgHI There has been keen interest in the use of magnesium as a potential neuroprotective intervention in perinatal medicine. Magnesium plays a critical role in the functioning of excitatory neurotransmitters, mostly at the postsynaptic level. It is a noncompetitive, voltage-dependent channel blocker acting on a modulatory site within the N-methyl-D-aspartate (NMDA) channel (1). This function is thought to allow magnesium to potentially block distal manifestations of the excitotoxic pathway. This is highly relevant inasmuch as excitatory neurotransmitters, such as glutamate, function as neurotoxins when in high concentrations in the brain extracellular fluid (ECF) (2). The latter occurs during hypoxia and/or ischemia due to excessive release of neurotransmitters as well as blockade of reuptake mechanisms (3). The high concentrations of excitatory transmitters stimulate surface receptors of neurons excessively and result in an influx of calcium, which in turn triggers a cascade of intracellular events culminating in tissue injury. There is specific interest in the neuroprotective effects of

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confidence: 86%

The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine

et al. 2004

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“…It is known that MgSO 4 rapidly crosses the placenta (25) and fetal blood brain barrier (26) blocking n-methyl-d-aspartate receptors (27) and glutamate receptors (28), receptors critically involved in neuronal death during hypoxic-ischemic injury. Whether these actions result in reduced neuronal excitation remains open to question (29). Recent evidence also supports a role for MgSO 4 in immunomodulation with in vitro exposure of neonatal monocytes to clinically relevant doses of MgSO 4 producing a reduction in both constitutive and toll-like receptor-stimulated TNFα and IL-6 gene and protein expression (8).…”

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confidence: 99%

Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics

2015

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“…Seven perinatal studies reported no improvement with MgSO 4 after HI, all after short to medium survival times (2-11 days) [20,21,24,28,29,30,31,32]. All of the rodent studies and 1 piglet study showing no benefit involved treatment after the insult [21,24,28,29,31,32].…”

Section: Analysis Strategymentioning

confidence: 99%

“…All of the rodent studies and 1 piglet study showing no benefit involved treatment after the insult [21,24,28,29,31,32]. In the study in near-term fetal lambs, MgSO 4 was infused from 2 h before umbilical cord occlusion and similarly showed no benefit [30]. …”

Section: Analysis Strategymentioning

confidence: 99%

Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review

et al. 2014

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There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO₄) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but that it has no effect on death or disability. Because of this inconsistency, it remains controversial whether MgSO₄ is clinically neuroprotective and, thus, it is unclear whether it would be appropriate to test MgSO₄ for treatment of encephalopathy in term infants. We therefore systematically reviewed the preclinical evidence for neuroprotection with MgSO₄ before or after hypoxic-ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The outcomes were highly inconsistent between studies. Although there were differences in dose and timing of administration, there was evidence that beneficial effects of MgSO₄ were associated with confounding mild hypothermia and, strikingly, the studies that included rigorous maintenance of environmental temperature or body temperature consistently suggested a lack of effect. On balance, these preclinical studies suggest that peripherally administered MgSO₄ is unlikely to be neuroprotective. Rigorous testing in translational animal models of perinatal HIE is needed before MgSO₄ should be considered in clinical trials for encephalopathy in term infants.

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Magnesium sulfate therapy during asphyxia in near-term fetal lambs does not compromise the fetus but does not reduce cerebral injury

Cited by 88 publications

References 24 publications

The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine

The Effects of Systemic Magnesium Sulfate Infusion on Brain Magnesium Concentrations and Energy State During Hypoxia-Ischemia in Newborn Miniswine

Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics

Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review

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