Magnesium as a Neuroprotective Agent: A Review of Its Use in the Fetus, Term Infant with Neonatal Encephalopathy, and the Adult Stroke Patient (original) (raw)
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Magnesium Sulfate: Fetal Neuroprotective Role in Reducing the Risk of Cerebral Palsy
Donald School Journal of Ultrasound in Obstetrics and Gynecology, 2013
Advances in perinatal and neonatal medicine have significantly improved survival rates of preterm infants. This improvement has been associated with substantial risk of neurodevelopmental impairments and with increased number of infants with special health care needs. Cerebral palsy is the most well known and potentially most disabling motor abnormality associated with prematurity. There has been limited progress in understanding the causes of cerebral palsy and in developing primary prevention strategies. Several studies have summarized the experimental evidence that supports possible neuroprotective effects of magnesium. Five randomized controlled trials of antenatal magnesium sulfate found a trend of reduced risk of cerebral palsy in preterm infants. Three meta-analyses using the data from these five trials found that magnesium sulfate given to women at risk of premature birth significantly reduced the risk of cerebral palsy without increasing the risk of perinatal or infant deat...
Magnesium Sulfate and Novel Therapies to Promote Neuroprotection
Clinics in Perinatology, 2019
Preterm delivery (PTD) is a major cause of neonatal morbidity and mortality, with surviving infants at risk for long-term neurologic sequelae. Although any birth occurring before the completion of 37 weeks' gestation is considered preterm, most serious harm occurs in the 16% of preterm deliveries occurring before 32 weeks' gestation. 1 Neurodevelopmental impairments can include cerebral palsy (CP), cognitive dysfunction, and sensory impairments (blindness and deafness). Cerebral palsy affects 2 per 1000 infants; however, the risk of CP is inversely proportional to gestational weight and age at delivery. Thus, the prevalence of CP is increased to 60 per 1000 infants in neonates weighing less than 1500 g 2 ; and approximately one-third of new CP cases are associated with delivery before 32 weeks' gestation. 3 Within the spectrum of neurologic impairment associated with PTD, CP has been used as the primary Disclosure: The authors have no financial interests to disclose.
Pharmacology research & perspectives, 2017
Clinical studies showed beneficial effects of magnesium sulfate regarding the risk of cerebral palsy. However, regimen protocols fluctuate worldwide and risks of adverse effects impacting the vascular system have been reported for human neonates, keeping open the question of the optimal dosing. Using clinically relevant concentrations and doses of magnesium sulfate, experiments consisted of characterizing, respectively, ex vivo and in vivo, the effects of magnesium sulfate on the nervous and vascular systems of mouse neonates by targeting neuroprotection, angiogenesis, and hemodynamic factors and in measuring, in human fetuses, the impact of a 4-g neuroprotective loading dose of magnesium sulfate on brain hemodynamic parameters. Preclinical experiments using cultured cortical slices from mouse neonates showed that the lowest and highest tested concentrations of magnesium sulfate were equally potent to prevent excitotoxic-induced cell death, cell edema, cell burst, and intracellular ...
Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application
Frontiers in Neurology, 2018
Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG). Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs), magnesium sulfate preconditioning decreased the induced lesions' sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h) to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.
Cureus, 2021
Background In Pakistan, the neonatal mortality rate is 41 per 1,000 live births and birth asphyxia is one of the leading causes of neonatal mortality and morbidity. The goal of this study was to determine whether postnatal magnesium sulfate therapy can improve short- and long-term neurological outcomes in term or near-term neonates with moderate-to-severe birth asphyxia. Methodology This prospective double-blind randomized controlled trial was conducted in the Neonatology Department of the Children’s Hospital & The Institute of Child Health, Lahore. A total of 62 neonates (31 in each group) were randomized to receive either three doses of magnesium sulfate infusion at 250 mg/kg per dose, 24 hours apart (treatment group), or three doses of injection 10% distilled water infusion at 3 mL/kg, 24 hours apart (placebo group). Both groups received similar supportive care. The neurodevelopmental assessment was done at six months of age using the ShaMaq Developmental Inventory. Results Demog...
Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis
Journal of Perinatology, 2013
Magnesium may have a role in neuroprotection in neonatal hypoxic-ischemic encephalopathy (HIE). The objective of this study was to systematically review the efficacy and safety of postnatal magnesium therapy in newborns with HIE. STUDY DESIGN: MEDLINE, EMBASE, CINAHL and CCRCT were searched for studies of magnesium for HIE. Randomized controlled trials that compared magnesium to control in newborns with HIE were selected. The primary outcome was a composite outcome of death or moderate-to-severe neurodevelopmental disability at 18 months. When appropriate, meta-analyses were conducted using random effects model and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULT: Five studies with sufficient quality were included. There was no difference in the primary outcome between the magnesium and the control groups (RR 0.81, 95% CI 0.36 to 1.84). There was significant reduction in the unfavorable short-term composite outcome (RR 0.48, 95% CI 0.30 to 0.77) but no difference in mortality (RR 1.39, 95% CI 0.85 to 2.27), seizures (RR 0.84, 95% CI 0.59 to 1.19) or hypotension (RR 1.28, 95% CI 0.69 to 2.38) between the magnesium and the control groups. CONCLUSION: The improvement in short-term outcomes without significant increase in side effects indicate the need for further trials to determine if there are long-term benefits of magnesium and to confirm its safety. Mortality was statistically insignificant between the magnesium and the control groups. However, the trend toward increase in mortality in the magnesium group is a major clinical concern and should be monitored closely in future trials.
Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017
Magnesium sulphate (MgSO) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO induces preconditioning in the immature brain. Therefore, we administered MgSO at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats. We found that MgSO treatment administered as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury, with maximal protection achieved by 1.1 mg/g MgSO administered 24 h before HI. As serum magnesium levels returned to baseline before the induction of HI, we ascribed this reduction in brain injury to preconditioning. Cerebral blood flow was unaffected, but mRNAs/miRNAs involved in mitochondrial function and metabolism were modulated by MgSO. Metabolomic analysis...
Journal of Child Science, 2021
Therapeutic hypothermia (TH) either by selective head cooling or whole-body cooling decreases brain damage and provide neuroprotection and reduced mortality rate in cases of moderate-to-severe hypoxia-ischemia encephalopathy (HIE) of newborns, especially if started at first 6 hours after birth. Also, management with adjuvant therapies like magnesium sulfate (MS) provides more neuroprotection. The interventional randomized controlled research aimed to assess short-term actions of TH as sole therapy and in combination with MS as a neuroprotective agent for the treatment of HIE newborn infants. A total of 36 full-terms and near-term infants delivered at Assiut University Children's Hospital and fulfilled HIE criteria were enrolled. They were divided equally into three groups; Group 1 (n = 12) received whole body cooling during first 6 hours of life as a sole therapy; Group 2 (n = 12) received whole body cooling in addition to MS as adjuvant therapy; Group 3 (n = 12) received suppor...