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Neuroprotective Effect of Long-term MgSO4 Administration After Cerebral Hypoxia-Ischemia in Newborn Rats Is Related to the Severity of Brain Damage

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Abstract

Previous studies have shown contradictory results regarding magnesium-mediated neuroprotection in animal models of perinatal asphyxia. The aim of this study is to investigate the e fects of MgSO4 postasphyxial treatment on hypoxia-ischemia (HI)—induced brain injury in neonatal rats and the possibility that this e fect is related to the severity of brain damage. Seven-day-old rats underwent unilateral carotid artery ligation followed by 1 or 2 hours of hypoxia (8% O2) and MgSO4 administration. Adenosine triphosphate/phosphocreatine and glutamate/glutamine measurements and neuropathological evaluation of the hippocampus were used to assess the e fects of HI and MgSO4. HI caused time-dependent changes in energy stores, amino acid concentrations, and brain damage. Administration of MgSO4 after 1 hour but not after 2 hours of hypoxia resulted in significant prevention of HI-induced brain injury. MgSO4 administration results in a significant protection against moderate HI-induced brain damage, whereas it fails to offer a similar effect against severe brain damage.

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References

  1. Volpe JJ Hypoxic-ischemic encephalopathy: biochemical and physiological aspects: In:Volpe JJ ed. Neurology of the Newborn. 4th ed. Philadelphia, PA:WB Saunders; 2001:217–267.

    Google Scholar 

  2. Delivoria-Papadopoulos M., Mishra OP Mechanisms of perinatal brain injury in the fetus and newborn. Ann N Y Acad Sci. 2000;900:159–168.

    Article  CAS  Google Scholar 

  3. Buonocore G., Perrone S. Biomarkers of hypoxic brain injury in the neonate. Clin Perinatol. 2004;31:107–116.

    Article  CAS  Google Scholar 

  4. Spandou E., Karkavelas G., Soubasi V., Augoustidou-Savvopoulou P., Loizidis T., Guiba-Tziampiri O. Effect of ketamine on hypoxic-ischemic brain damage in newborn rats. Brain Res. 1999;819:1–7.

    Article  CAS  Google Scholar 

  5. Peeters-Scholte C., Koster J., van den Tweel E., et al. Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia. Pediatr Res. 2003;54:516–522.

    Article  CAS  Google Scholar 

  6. Nowak L., Bregestovsi P., Ascher P., et al. Magnesium gates glutamate-activated channels in mouse central neurons. Nature. 1984;307:462–465.

    Article  CAS  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. Hoffman DJ, Marro PJ, McGowan JE, et al. Protective effect of MgSO4 infusion on NMDA receptor binding characteristics during cerebral cortical hypoxia in the newborn piglet. Brain Res. 1994;644:144–149.

    Article  CAS  Google Scholar 

  9. Levene MI, Blennow M., Whitelaw A., et al. Acute effects of two different doses of magnesium sulphate in infants with birth asphyxia. Arch Dis Child. 1995;73:F174–F177.

    Article  CAS  Google Scholar 

  10. de Haan HH, Gunn AJ, Williams CE, et al. Magnesium sulfate therapy during asphyxia in near term fetal lambs does not compromise the fetus but does not reduce cerebral injury. Am J Obstet Gynecol. 1997;176:18–27.

    Article  Google Scholar 

  11. Leviton A., Paneth N., Susser M., et al. Maternal receipt of magnesium sulfate does not seem to reduce the risk of neonatal white matter damage. Pediatrics. 1997;99:E2.

    Article  CAS  Google Scholar 

  12. Penrice J., Amess PN, Punwani S., et al. Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet. Pediatr Res. 1997; 41:443–447.

    Article  CAS  Google Scholar 

  13. Galvin KA, Oorschot E. Postinjury magnesium sulfate treatment is not markedly neuroprotective for striatal medium spiny neurons after perinatal hypoxia/ischemia in the rat. Pediatr Res. 1998;44:740–745.

    Article  CAS  Google Scholar 

  14. Sameshima H., Ota A., Ikenoue T. Pretreatment with magnesium sulfate protects against hypoxic-ischemic brain injury but postasphyxial treatment worsens brain damage in seven-day-old rats. Am J Obstet Gynecol. 1999;180:725–730.

    Article  CAS  Google Scholar 

  15. Sameshima H., Ikenoue T. Long-term magnesium sulfate treatment protects against hypoxic-ischemic brain injury in seven-day-old rats. Am J Obstet Gynecol. 2001;184:185–190.

    Article  CAS  Google Scholar 

  16. Sameshima H., Ikenoue T. Effect of long-term, postasphyxial administration of magnesium sulfate on immunostaining of microtubule-associated protein-2 and activated caspace-3 in 7-day-old rat brain. J Soc Gynecol Invest. 2002;9:203–209.

    Article  CAS  Google Scholar 

  17. Greenwood K., Cox P., Mehmet H., et al. Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage. Pediatr Res. 2000;48:346–350.

    Article  CAS  Google Scholar 

  18. Ichiba H., Tamai H., Negishi H., et al. Randomized controlled trial of magnesium sulfate infusion for severe birth asphyxia. Pediatr Int. 2002;44:505–509.

    Article  CAS  Google Scholar 

  19. Ichiba H., Yokoi T., Tamai H., et al. Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate. Pediatr Int. 2006;48:70–75.

    Article  CAS  Google Scholar 

  20. Groenendaal F., Rademaker Cma, Toet MC, et al. Effects of magnesium sulfate on amplitude-integrated continuous EEG in asphyxiated term neonates. Acta Paediatr. 2002;91:1073–1077.

    Article  CAS  Google Scholar 

  21. Hallak M., Hotra JW, Kupsky WJ Magnesium sulfate protection on fetal rat brain from severe maternal hypoxia. Obstet Gynecol. 2000;96:124–128.

    CAS  PubMed  Google Scholar 

  22. Rice JE, Vannucci RC, Brierley JB The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981;9:131–141.

    Article  Google Scholar 

  23. Lamprecht W. Creatine phosphate. In: Bergmeyer HU, ed. Methods of Enzymatic Analysis. New York, NY:Academic Press; 1974:1777–1781.

    Chapter  Google Scholar 

  24. Sherwood NH, Timiras PS A Stereotaxic Atlas of the Developing Rat Brain. Berkeley:SAGE Publications; 1970.

    Google Scholar 

  25. Wu TJ, Teng RJ, Yau K-IT. Persistent pulmonary hypertension of the newborn treated with magnesium sulfate in premature neonates. Pediatrics. 1995;96:472–474.

    CAS  PubMed  Google Scholar 

  26. Vande Linde AM, Chopp M., Chen H., et al. Chronic changes in the brain Mg 2+ concentration after forebrain ischemia in the rat. Metab Brain Dis. 1991;6:199–206.

    Article  Google Scholar 

  27. Choi D., Rothman SM The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann Rev Neurosci. 1990;13:171–182.

    Article  CAS  Google Scholar 

  28. Monyer H., Burnashev N., Laurie D., Sakmann B., Seeburg PH Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994;12:529–540.

    Article  CAS  Google Scholar 

  29. Khashaba MT, Shouman BO, Shaltout AA, et al. Excitatory amino acids and magnesium sulfate in neonatal asphyxia. Brain Dev. 2006;28:375–379.

    Article  Google Scholar 

  30. Blumberg RM, Cady EB, Wigglesworth JS, Mc Kenzie JE, Edwards AD. Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain. Exp Brain Res. 1997;113:130–137.

    Article  CAS  Google Scholar 

  31. Nishio A., Gebrewold A., Altura BT, Altura BM Comparative vasodilator effects of magnesium salts on rat mesenteric arterioles and venules. Arch Int Pharmacodyn Therap. 1989;298:139–163.

    CAS  Google Scholar 

  32. Ravishankar S., Ashraf QM, Fritz K., Mishra OP, Delivoria-Paapdopoulos M. Expression of Bax and Bcl-2 proteins during hypoxia in cerebral cortical neuronal nuclei of newborn piglets: effect of administration of magnesium sulfate. Brain Res. 2001;901:23–29.

    Article  CAS  Google Scholar 

  33. 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.

    Article  CAS  Google Scholar 

  34. Mami AG, Ballesteros J., Mishra OP, Delivoria-Papadopoulos M. Effects of magnesium sulfate administration during hypoxia on Ca2+ influx and IP3 receptor modification in cerebral cortical neuronal nuclei of newborn piglets. Neurochem Res. 2006;31:63–70.

    Article  CAS  Google Scholar 

  35. Marret S., Gressens P., Gadisseux JF, Ervard 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.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece

    Evangelia Spandou PhD, Stamatia Papoutsopoulou PhD, Theodoros Loizidis MD, PhD, Anastasia Pazaiti MD, PhD & Olympia Guiba-Tziampiri MD, PhD

  2. Department of Neonatology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Vassiliki Soubasi MD, PhD

  3. Department of Pediatrics, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Persefoni Augoustides-Savvopoulou MD, PhD

  4. Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    George Karkavelas MD, PhD

Authors
  1. Evangelia Spandou PhD
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  2. Vassiliki Soubasi MD, PhD
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  3. Stamatia Papoutsopoulou PhD
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  4. Persefoni Augoustides-Savvopoulou MD, PhD
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  5. Theodoros Loizidis MD, PhD
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  6. Anastasia Pazaiti MD, PhD
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  7. George Karkavelas MD, PhD
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  8. Olympia Guiba-Tziampiri MD, PhD
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Correspondence to Evangelia Spandou PhD.

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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. 14, 667–677 (2007). https://doi.org/10.1177/1933719107305864

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  • DOI: https://doi.org/10.1177/1933719107305864

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