Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies: A systematic review

Robert Galinsky, Laura Bennet, Floris Groenendaal, Christopher A. Lear, Sidhartha Tan, Frank Van Bel, Sandra E. Juul, Nicola J. Robertson, Carina Mallard, Alistair J. Gunn

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalDevelopmental Neuroscience
Volume36
Issue number2
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Asphyxia
  • Brain injury
  • Cerebral palsy
  • Hypoxic-ischemic encephalopathy
  • Magnesium sulfate
  • Neuroprotection

Cite this

Galinsky, Robert ; Bennet, Laura ; Groenendaal, Floris ; Lear, Christopher A. ; Tan, Sidhartha ; Van Bel, Frank ; Juul, Sandra E. ; Robertson, Nicola J. ; Mallard, Carina ; Gunn, Alistair J. / Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies : A systematic review. In: Developmental Neuroscience. 2014 ; Vol. 36, No. 2. pp. 73-82.
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abstract = "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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Galinsky, R, Bennet, L, Groenendaal, F, Lear, CA, Tan, S, Van Bel, F, Juul, SE, Robertson, NJ, Mallard, C & Gunn, AJ 2014, 'Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies: A systematic review' Developmental Neuroscience, vol. 36, no. 2, pp. 73-82. https://doi.org/10.1159/000362206

Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies : A systematic review. / Galinsky, Robert; Bennet, Laura; Groenendaal, Floris; Lear, Christopher A.; Tan, Sidhartha; Van Bel, Frank; Juul, Sandra E.; Robertson, Nicola J.; Mallard, Carina; Gunn, Alistair J.

In: Developmental Neuroscience, Vol. 36, No. 2, 01.01.2014, p. 73-82.

Research output: Contribution to journalReview ArticleResearchpeer-review

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T1 - Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies

T2 - A systematic review

AU - Galinsky, Robert

AU - Bennet, Laura

AU - Groenendaal, Floris

AU - Lear, Christopher A.

AU - Tan, Sidhartha

AU - Van Bel, Frank

AU - Juul, Sandra E.

AU - Robertson, Nicola J.

AU - Mallard, Carina

AU - Gunn, Alistair J.

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