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TitlePossible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and PostTreatment in a Neonatal Hypoxic-Ischemic Rat Model.Author(s)Cetinkaya M, Alkan T, Ozyener F, Kafa IM, Kurt MA, Koksal N InstitutionDepartment of Pediatrics, Division of Neonatology, Faculty of Medicine, Uludag University, Bursa, Turkey.SourceNeonatology 2010 Dec 4; 99(4):302-310.AbstractBackground: Perinatal hypoxia-ischemia is a major cause of mortality and long-term neurological deficits. Objectives: The objective of this study was to compare the effects of two neuroprotective agents; magnesium sulfate and melatonin, administered alone or in combination, on brain infarct volume and TUNEL positivity in a neonatal hypoxic-ischemic (HI) rat model. Methods: After being anesthetized, 7-day-old pups (n = 80) underwent ischemia followed by exposure to hypoxia for 2 h. The pups were then divided equally and randomly into 4 groups in order to receive the vehicle (saline, control group), magnesium sulfate, melatonin or a combination of magnesium sulfate and melatonin. Treatments were administered intraperitoneally three times; the first being just before ischemia, the second after hypoxia and the third 24 h after the second dose. The pups were sacrificed on postnatal day 10, their brains harvested and evaluated for infarct volume and neuronal apoptosis. Results: Percent infarcted brain volume was significantly reduced in pups receiving the drugs (either magnesium sulfate, melatonin or their combination) compared with those receiving the vehicle. In addition, TUNEL staining showed markedly reduced numbers of TUNEL-positive cells per unit area in the CA1, CA3 and dentate gyrus regions of the hippocampus and in the cortex. However, no statistically significant differences were found regarding percent infarcted brain volume and number of TUNELpositive cells among the drug-treated groups. Conclusions: Magnesium sulfate and melatonin, two agents acting at different stages of HI brain damage, administered either alone or in combination, significantly reduced the percent infarcted brain volume and TUNEL positivity, suggesting that these agents may confer a possible benefit in the treatment of infants with HI encephalopathy.LanguageENGPub Type(s)JOURNAL ARTICLE PubMed ID21135566

http://www.ncbi.nlm.nih.gov/pubmed/7838646?dopt=Abstract

Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants?
Nelson KB, Grether JK. Neuroepidemiology Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, MD. Comment in:

Pediatrics. 1996 May;97(5):780-2.

Abstract
OBJECTIVES: To investigate whether in utero exposure to magnesium sulfate (MgSO4) was associated with a lower prevalence of cerebral palsy (CP) in infants born weighing < 1500 g. DESIGN: Singleton infants weighing < 1500 g at birth (very low birthweight, VLBW) and surviving to 3 years with moderate or severe congenital CP were identified among 155,636 children born 1983 through 1985 in four California counties. VLBW children with CP were compared with randomly selected VLBW control survivors with respect to whether their mothers received MgSO4 to prevent convulsions in preeclampsia or as a tocolytic agent, and other information abstracted from labor and delivery records. RESULTS: During the admission for delivery, 7.1% of the 42 VLBW infants with later CP and 36% of the 75 VLBW controls were exposed to MgSO4 (odds ratio (OR) .14, 95% confidence interval (CI) .05, .51). The overall association of MgSO4 with reduced risk of CP was also observed in the subgroup of infants born to women who were not preeclamptic (OR .25, CI .08, .97). Infants with CP were less often exposed antenatally to MgSO4 whether or not there was cotreatment with non-MgSO4 tocolytics (other tocolytics administered, OR for MgSO4 exposure .23, CI .06, 1.2; other tocolytics not administered, OR for MgSO4 .08, CI .02, .68), or antenatal corticosteroids (steroids given, OR for MgSO4 exposure .24, CI .06, 1.3; steroids not given, OR for MgSO4, .08, CI .02, .72). Apparent benefit of magnesium was observed in the presence or absence of a variety of characteristics of pregnancies, births, and infants. CONCLUSION: In this observational study, in utero exposure to MgSO4 was more frequent in controls than in children with CP, suggesting a protective effect of MgSO4 against CP in these VLBW infants. PMID: 7838646 [PubMed - indexed for MEDLINE]

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