American Journal of Obstetrics & Gynecology
Volume 202, Issue 3 , Pages 292.e1-292.e9 , March 2010

Magnesium sulfate reduces inflammation-associated brain injury in fetal mice

Presented orally at the 30th Annual Scientific Meeting of the Society for Maternal-Fetal Medicine, Chicago, IL, Feb. 1-6, 2010. The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community.

  • Irina Burd, MD, PhD

      Affiliations

    • Corresponding Author InformationReprints: Irina D. Burd, MD, PhD, Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, 1353 Biomedical Research Bldg. II/III, 421 Curie Blvd., Philadelphia, PA 19104-6142
    • ,
  • Kelsey Breen, BS
    • ,
  • Alexander Friedman, MD, MPH
    • ,
  • Jinghua Chai, MD
    • ,
  • Michal A. Elovitz, MD

Received 21 November 2009 ,Revised 24 December 2009 ,Accepted 14 January 2010.

References 

  1. Koman LA, Smith BP, Shilt JS. Cerebral palsy. Lancet. 2004;363:1619–1631
  2. Winter S, Autry A, Boyle C, Yeargin-Allsopp M. Trends in the prevalence of cerebral palsy in a population-based study. Pediatrics. 2002;110:1220–1225
  3. Yeargin-Allsopp M, Van Naarden Braun K, et al. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration. Pediatrics. 2008;121:547–554
  4. Jacobsson B, Hagberg G, Hagberg B, Ladfors L, Niklasson A, Hagberg H. Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors. Acta Paediatr. 2002;91:946–951
  5. Nelson KB, Grether JK. Causes of cerebral palsy. Curr Opin Pediatr. 1999;11:487–491
  6. Tyson JE, Gilstrap LC. Hope for perinatal prevention of cerebral palsy. JAMA. 2003;290:2730–2732
  7. Costantine MM, Weiner SJ. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol. 2009;114:354–364
  8. Doyle LW, Crowther CA, Middleton P, Marret S. Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol. 2009;113:1327–1333
  9. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;CD004661
  10. Crowther CA, Hiller JE, Doyle LW, Haslam RR. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA. 2003;290:2669–2676
  11. Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008;359:895–905
  12. Mittendorf R, Pryde PG. A review of the role for magnesium sulphate in preterm labour. BJOG. 2005;112(suppl 1):84–88
  13. Doyle LW, Crowther CA, Middleton P, Marret S. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2007;CD004661
  14. Dribben WH, Creeley CE, Wang HH, Smith DJ, Farber NB, Olney JW. High dose magnesium sulfate exposure induces apoptotic cell death in the developing neonatal mouse brain. Neonatology. 2009;96:23–32
  15. Spandou E, Soubasi V, Papoutsopoulou S, et al. Neuroprotective effect of long-term MgSO4 administration after cerebral hypoxia-ischemia in newborn rats is related to the severity of brain damage. Reprod Sci. 2007;14:667–677
  16. Marret S, Gressens P, Gadisseux JF, Evrard P. Prevention by magnesium of excitotoxic neuronal death in the developing brain: an animal model for clinical intervention studies. Dev Med Child Neurol. 1995;37:473–484
  17. Imer M, Omay B, Uzunkol A, et al. Effect of magnesium, MK-801 and combination of magnesium and MK-801 on blood-brain barrier permeability and brain edema after experimental traumatic diffuse brain injury. Neurol Res. 2009;31:977–981
  18. Kaya M, Kucuk M, Kalayci RB, et al. Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats. Can J Physiol Pharmacol. 2001;79:793–798
  19. McDonald JW, Silverstein FS, Johnston MV. Magnesium reduces N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats. Neurosci Lett. 1990;109:234–238
  20. Enomoto T, Osugi T, Satoh H, McIntosh TK, Nabeshima T. Pre-injury magnesium treatment prevents traumatic brain injury-induced hippocampal ERK activation, neuronal loss, and cognitive dysfunction in the radial-arm maze test. J Neurotrauma. 2005;22:783–792
  21. Turkyilmaz C, Turkyilmaz Z, Atalay Y, Soylemezoglu F, Celasun B. Magnesium pre-treatment reduces neuronal apoptosis in newborn rats in hypoxia-ischemia. Brain Res. 2002;955:133–137
  22. Ernst LM, Gonzalez J, Ofori E, Elovitz M. Inflammation-induced preterm birth in a murine model is associated with increases in fetal macrophages and circulating erythroid precursors. Pediatr Dev Pathol. 2009;Epub ahead of print
  23. Elovitz MA, Mrinalini C, Sammel MD. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr Res. 2006;59:50–55
  24. Burd I, Chai J, Gonzalez J, et al. Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth. Am J Obstet Gynecol. 2009;201:279.e1;-8
  25. Burd I, Bentz A, Gonzalez J, et al. Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain. J Neurosci Res. In press.
  26. Elovitz MA, Wang Z, Chien EK, Rychlik DF, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol. 2003;163:2103–2111
  27. Yoon BH, Park CW, Chaiworapongsa T. Intrauterine infection and the development of cerebral palsy. BJOG. 2003;110(suppl 20):124–127
  28. Hallak M, Hotra JW, Custodio D, Kruger ML. Magnesium prevents seizure-induced reduction in excitatory amino acid receptor (kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) binding in pregnant rat brain. Am J Obstet Gynecol. 2000;183:793–798
  29. Hallak M, Hotra JW, Kupsky WJ. Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia. Obstet Gynecol. 2000;96:124–128
  30. Golan H, Kashtuzki I, Hallak M, Sorokin Y, Huleihel M. Maternal hypoxia during pregnancy induces fetal neurodevelopmental brain damage: partial protection by magnesium sulfate. J Neurosci Res. 2004;78:430–441
  31. Hallak M, Cotton DB. Transfer of maternally administered magnesium sulfate into the fetal compartment of the rat: assessment of amniotic fluid, blood, and brain concentrations. Am J Obstet Gynecol. 1993;169:427–431
  32. Brewer GJ. Serum-free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus. J Neurosci Res. 1995;42:674–683
  33. Brewer GJ, Torricelli JR, Evege EK, Price PJ. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. J Neurosci Res. 1993;35:567–576
  34. Monnerie H, Shashidhara S, Le Roux PD. Effect of excess extracellular glutamate on dendrite growth from cerebral cortical neurons at 3 days in vitro: Involvement of NMDA receptors. J Neurosci Res. 2003;74:688–700
  35. Poolos NP. Seeing the forest and the trees: dendritic injury after status epilepticus. Epilepsy Curr. 2008;8:77–79
  36. Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005;352:9–19
  37. Anderson P, Doyle LW. Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA. 2003;289:3264–3272
  38. Hack M, Taylor HG, Drotar D, et al. Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birthweight in the 1990s. JAMA. 2005;294:318–325
  39. Costeloe K. EPICure: facts and figures: why preterm labour should be treated. BJOG. 2006;113(suppl 3):10–12
  40. Wood NS, Costeloe K, Gibson AT, Hennessy EM, Marlow N, Wilkinson AR. The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth. Arch Dis Child Fetal Neonatal Ed. 2005;90:F134–F140
  41. Limperopoulos C, Bassan H, Sullivan NR, et al. Positive screening for autism in ex-preterm infants: prevalence and risk factors. Pediatrics. 2008;121:758–765
  42. Schendel D, Bhasin TK. Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities. Pediatrics. 2008;121:1155–1164
  43. Brimacombe M, Ming X, Lamendola M. Prenatal and birth complications in autism. Matern Child Health J. 2007;11:73–79
  44. Paintlia MK, Paintlia AS, Barbosa E, Singh I, Singh AK. N-acetylcysteine prevents endotoxin-induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain. J Neurosci Res. 2004;78:347–361
  45. Cai Z, Pan ZL, Pang Y, Evans OB, Rhodes PG. Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopolysaccharide administration. Pediatr Res. 2000;47:64–72
  46. Rousset CI, Chalon S, Cantagrel S, et al. Maternal exposure to LPS induces hypomyelination in the internal capsule and programmed cell death in the deep gray matter in newborn rats. Pediatr Res. 2006;59:428–433
  47. Patterson PH. Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol. 2002;12:115–118
  48. Reijneveld SA, de Kleine MJ, van Baar AL, et al. Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years. Arch Dis Child Fetal Neonatal Ed. 2006;91:F423–F428
  49. Anderson PJ, Doyle LW. Cognitive and educational deficits in children born extremely preterm. Semin Perinatol. 2008;32:51–58
  50. Shum D, Neulinger K, O'Callaghan M, Mohay H. Attentional problems in children born very preterm or with extremely low birth weight at 7-9 years. Arch Clin Neuropsychol. 2008;23:103–112
  51. Farooqi A, Hagglof B, Sedin G, Gothefors L, Serenius F. Mental health and social competencies of 10- to 12-year-old children born at 23 to 25 weeks of gestation in the 1990s: a Swedish national prospective follow-up study. Pediatrics. 2007;120:118–133
  52. Limperopoulos C, Bassan H, Gauvreau K, et al. Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?. Pediatrics. 2007;120:584–593
  53. Leviton A, Gressens P. Neuronal damage accompanies perinatal white-matter damage. Trends Neurosci. 2007;30:473–478
  54. Rademaker KJ, Uiterwaal CS, Beek FJ, et al. Neonatal cranial ultrasound versus MRI and neurodevelopmental outcome at school age in children born preterm. Arch Dis Child Fetal Neonatal Ed. 2005;90:F489–F493
  55. Kuban KC, Allred EN, O'Shea TM, et al. Cranial ultrasound lesions in the NICU predict cerebral palsy at age 2 years in children born at extremely low gestational age. J Child Neurol. 2009;24:63–72
  56. Abuhatzira L, Shemer R, Razin A. MeCP2 involvement in the regulation of neuronal alpha-tubulin production. Hum Mol Genet. 2009;18:1415–1423
  57. Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM. Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry. 2006;59:468–476
  58. Hu VW, Frank BC, Heine S, Lee NH, Quackenbush J. Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics. 2006;7:118
  59. Fatemi SH. The role of Reelin in pathology of autism. Mol Psychiatry. 2002;7:919–920
  60. Fatemi SH, Earle J, Kanodia R, et al. Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol. 2002;22:25–33
  61. Fatemi SH, Halt AR, Realmuto G, et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol. 2002;22:171–175
  62. Gonzalez JM, Ofori E, Burd I, Chai J, Scholler N, Elovitz MA. Maternal mortality from systemic illness: unraveling the contribution of the immune response. Am J Obstet Gynecol. 2009;200:430.e1;-8
  63. Dammann O, Leviton A. Inflammatory brain damage in preterm newborns—dry numbers, wet lab, and causal inferences. Early Hum Dev. 2004;79:1–15
  64. Bell MJ, Hallenbeck JM. Effects of intrauterine inflammation on developing rat brain. J Neurosci Res. 2002;70:570–579
  65. Strecker GJ, Jackson MB, Dudek FE. Blockade of NMDA-activated channels by magnesium in the immature rat hippocampus. J Neurophysiol. 1994;72:1538–1548

 Cite this article as: Burd I, Breen K, Friedman A, et al. Magnesium sulfate reduces inflammation-associated brain injury in fetal mice. Am J Obstet Gynecol 2010;202:292.e1-9.

 Supported by National Institutes of Health Grant 5-R01-HD046544-0 (M.A.E.) and in part by the ABOG/AAOGF scholarship (I.B.).

PII: S0002-9378(10)00033-5

doi: 10.1016/j.ajog.2010.01.022

American Journal of Obstetrics & Gynecology
Volume 202, Issue 3 , Pages 292.e1-292.e9 , March 2010

Article Tools

* Image Usage & Resolution