Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015 (2015), Article ID 257139, 14 pages
http://dx.doi.org/10.1155/2015/257139
Review Article

Neuroprotection in Preterm Infants

Marienhaus Klinikum St. Elisabeth, Department of Obstetrics and Gynecology, 56564 Neuwied, Germany

Received 14 October 2014; Accepted 22 December 2014

Academic Editor: Stefan Rimbach

Copyright © 2015 R. Berger and S. Söder. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Neonatal data from the German federal states (BQS Bundesauswertung 2008, Datensatzversion 16/1 2008 11.0. Datenbankstand 15.03.2009. 658.200 Datensätze).
  2. J. J. Volpe, Neurology of the Newborn, WB Saunders, 1995.
  3. G. Hambleton and J. S. Wigglesworth, “Origin of intraventricular haemorrhage in the preterm infant,” Archives of Disease in Childhood, vol. 51, no. 9, pp. 651–659, 1976. View at Publisher · View at Google Scholar · View at Scopus
  4. D. M. Moody, W. R. Brown, V. R. Challa, and S. M. Block, “Alkaline phosphatase histochemical staining in the study of germinal matrix hemorrhage and brain vascular morphology in a very-low-birth-weight neonate,” Pediatric Research, vol. 35, no. 4, pp. 424–430, 1994. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. Nakamura, T. Okudera, S. Fukuda, and T. Hashimoto, “Germinal matrix hemorrhage of venous origin in preterm neonates,” Human Pathology, vol. 21, no. 10, pp. 1059–1062, 1990. View at Publisher · View at Google Scholar · View at Scopus
  6. K. C. K. Kuban and F. H. Gilles, “Human telencephalic angiogenesis,” Annals of Neurology, vol. 17, no. 6, pp. 539–548, 1985. View at Publisher · View at Google Scholar · View at Scopus
  7. K. E. Pape and Wigglesworth, Haemorrhage, Ischemia and the Perinatal Brain, J. B. Lippincott, Philadelphia, Pa, USA, 1979.
  8. M. Funato, H. Tamai, K. Noma et al., “Clinical events in association with timing of intraventricular hemorrhage in preterm infants,” The Journal of Pediatrics, vol. 121, no. 4, pp. 614–619, 1992. View at Publisher · View at Google Scholar · View at Scopus
  9. R. N. Goldberg, D. Chung, S. L. Goldman, and E. Bancalari, “The association of rapid volume expansion and intraventricular hemorrhage in the preterm infant,” The Journal of Pediatrics, vol. 96, no. 6, pp. 1060–1063, 1980. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Jensen, V. Klingmuller, W. Kunzel, and S. Sefkow, “The risk of brain haemorrhage in preterms- and in mature newborns-infants,” Geburtshilfe und Frauenheilkunde, vol. 52, no. 1, pp. 6–20, 1992. View at Publisher · View at Google Scholar · View at Scopus
  11. D. W. A. Milligan, “Failure of autoregulation and intraventricular haemorrhage in preterm infants,” The Lancet, vol. 1, no. 8174, pp. 896–898, 1980. View at Google Scholar · View at Scopus
  12. R. Berger, S. Bender, S. Sefkow, V. Klingmüller, W. Künzel, and A. Jensen, “Peri/intraventricular haemorrhage: a cranial ultrasound study on 5286 neonates,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 75, no. 2, pp. 191–203, 1997. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Amato, J. C. Fauchere, and U. Hermann Jr., “Coagulation abnormalities in low birth weight infants with peri-intraventricular hemorrhage,” Neuropediatrics, vol. 19, no. 3, pp. 154–157, 1988. View at Publisher · View at Google Scholar · View at Scopus
  14. B. A. Lupton, A. Hill, M. F. Whitfield, C. J. Carter, L. D. Wadsworth, and E. H. Roland, “Reduced platelet count as a risk factor for intraventricular hemorrhage,” The American Journal of Diseases of Children, vol. 142, no. 11, pp. 1222–1224, 1988. View at Google Scholar · View at Scopus
  15. A. Shirahata, T. Nakamura, M. Shimono, M. Kaneko, and S. Tanaka, “Blood coagulation findings and the efficacy of factor XIII concentrate in premature infants with intracranial hemorrhages,” Thrombosis Research, vol. 57, no. 5, pp. 755–763, 1990. View at Publisher · View at Google Scholar · View at Scopus
  16. J. C. Larroche, Developmental Pathology of the Neonate, Excerpta Medica, New York, NY, USA, 1997.
  17. M. G. Norman, “Perinatal brain damage,” Perspectives in Pediatric Pathology, vol. 4, pp. 41–92, 1978. View at Google Scholar · View at Scopus
  18. L. S. de Vries, J. S. Wigglesworth, R. Regev, and L. M. S. Dubowitz, “Evolution of periventricular leukomalacia during the neonatal period and infancy: correlation of imaging and postmortem findings,” Early Human Development, vol. 17, no. 2-3, pp. 205–219, 1988. View at Publisher · View at Google Scholar · View at Scopus
  19. P. L. Hope, S. J. Gould, S. Howard, P. A. Hamilton, A. M. L. Costello, and E. O. R. Reynolds, “Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants,” Developmental Medicine & Child Neurology, vol. 30, no. 4, pp. 457–471, 1988. View at Google Scholar · View at Scopus
  20. N. Paneth, R. Rudelli, W. Monte et al., “White matter necrosis in very low birth weight infants: neuropathologic and ultrasonographic findings in infants surviving six days or longer,” The Journal of Pediatrics, vol. 116, no. 6, pp. 975–984, 1990. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Dambska, M. Laure-Kamionowska, and B. Schmidt-Sidor, “Early and late neuropathological changes in perinatal white matter damage,” Journal of Child Neurology, vol. 4, no. 4, pp. 291–298, 1989. View at Publisher · View at Google Scholar · View at Scopus
  22. S. M. De la Monte, F. I. Hsu, E. T. Hedley-Whyte, and W. Kupsky, “Morphometric analysis of the human infant brain: effects of intraventricular hemorrhage and periventricular leukomalacia,” Journal of Child Neurology, vol. 5, no. 2, pp. 101–110, 1990. View at Publisher · View at Google Scholar · View at Scopus
  23. F. H. Gilles and S. F. Murphy, “Perinatal telencephalic leucoencephalopathy,” Journal of Neurology Neurosurgery and Psychiatry, vol. 32, no. 5, pp. 404–413, 1969. View at Publisher · View at Google Scholar · View at Scopus
  24. F. H. Gilles, A. Leviton, and E. C. Dooling, The Developing Human Brain: Growth and Epidemiologic Neuropathology, John Wright PSG, Boston, Mass, USA, 1983.
  25. A. Quasebarth, Periventrikuläre Leukomalazie und Perinatale Telenzephale Leukoenzephalopathie. Ein und dieselbe Krankheit? Eine neuropathologische Studie anhand von 10 Falldarstellungen, Goethe University Frankfurt, Frankfurt, Germany, 2001.
  26. J. L. De Reuck, “Cerebral angioarchitecture and perinatal brain lesions in premature and full-term infants,” Acta Neurologica Scandinavica, vol. 70, no. 6, pp. 391–395, 1984. View at Google Scholar · View at Scopus
  27. L. B. Rorke, “Anatomical features of the developing brain implicated in pathogenesis of hypoxic-ischemic injury,” Brain Pathology, vol. 2, no. 3, pp. 211–221, 1992. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Takashima, D. L. Armstrong, and L. E. Becker, “Subcortical leukomalacia. Relationship to development of the cerebral sulcus and its vascular supply,” Archives of Neurology, vol. 35, no. 7, pp. 470–472, 1978. View at Publisher · View at Google Scholar · View at Scopus
  29. W. Szymonowicz, A. M. Walker, V. Y. H. Yu, M. L. Stewart, J. Cannata, and L. Cussen, “Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near-term, and newborn lamb,” Pediatric Research, vol. 28, no. 4, pp. 361–366, 1990. View at Publisher · View at Google Scholar · View at Scopus
  30. O. Dammann and A. Leviton, “Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn,” Pediatric Research, vol. 42, no. 1, pp. 1–8, 1997. View at Publisher · View at Google Scholar · View at Scopus
  31. S. K. Sinha, J. M. Davies, D. G. Sims, and M. L. Chiswick, “Relation between periventricular haemorrhage and ischaemic brain lesions diagnosed by ultrasound in very pre-term infants,” The Lancet, vol. 2, no. 8465, pp. 1154–1156, 1985. View at Google Scholar · View at Scopus
  32. U. Verma, N. Tejani, S. Klein et al., “Obstetric antecedents of intraventricular hemorrhage periventricular leukomalacia in the low-birth-weight neonate,” The American Journal of Obstetrics and Gynecology, vol. 176, no. 2, pp. 275–281, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. R. Romero, Z. A. Savasan, T. Chaiworapongsa et al., “Hematologic profile of the fetus with systemic inflammatory response syndrome,” Journal of Perinatal Medicine, vol. 40, no. 1, pp. 19–32, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Garnier, A. Coumans, R. Berger, A. Jensen, and T. H. M. Hasaart, “Endotoxemia severely affects circulation during normoxia and asphyxia in immature fetal sheep,” Journal of the Society for Gynecologic Investigation, vol. 8, no. 3, pp. 134–142, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Garnier, A. B. C. Coumans, A. Jensen, T. H. M. Hasaart, and R. Berger, “Infection-related perinatal brain injury: the pathogenic role of impaired fetal cardiovascular control,” Journal of the Society for Gynecologic Investigation, vol. 10, no. 8, pp. 450–459, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. H. N. Liu, B. I. Giasson, W. E. Mushynski, and G. Almazan, “AMPA receptor-mediated toxicity in oligodendrocyte progenitors involves free radical generation and activation of JNK, calpain and caspase 3,” Journal of Neurochemistry, vol. 82, no. 2, pp. 398–409, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. A. B. C. Coumans, J. Middelanis, Y. Garnier et al., “Intracisternal application of endotoxin enhances the susceptibility to subsequent hypoxic-ischemic brain damage in neonatal rats,” Pediatric Research, vol. 53, no. 5, pp. 770–775, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Feldhaus, I. D. Dietzel, R. Heumann, and R. Berger, “Effects of interferon-γ and tumor necrosis factor-α on survival and differentiation of oligodendrocyte progenitors,” Journal of the Society for Gynecologic Investigation, vol. 11, no. 2, pp. 89–96, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. W. Wu and J. M. Colford, “Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis,” Journal of the American Medical Association, vol. 284, no. 11, pp. 1417–1424, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. J. G. Shatrov, S. C. Birch, L. T. Lam, J. A. Quinlivan, S. McIntyre, and G. L. Mendz, “Chorioamnionitis and cerebral palsy: a meta-analysis,” Obstetrics & Gynecology, vol. 116, no. 2, part 1, pp. 387–392, 2010. View at Publisher · View at Google Scholar
  41. V. T. Guinto, B. De Guia, M. R. Festin, and T. Dowswell, “Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy,” Cochrane Database of Aystematic Reviews, vol. 9, Article ID CD007855, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. P. Brocklehurst, A. Gordon, E. Heatley, and S. J. Milan, “Antibiotics for treating bacterial vaginosis in pregnancy,” Cochrane Database of Systematic Reviews, Article ID CD000262, 2013. View at Publisher · View at Google Scholar
  43. D. Subtil, G. Brabant, E. Tilloy et al., “Early clindamycin for bacterial vaginosis in low-risk pregnancy: the PREMEVA1 randomized, multicenter, double-blind, placebo-controlled trial,” American Journal of Obstetrics & Gynecology, vol. 210, no. 1, supplement, p. S3, 2014. View at Publisher · View at Google Scholar
  44. E. B. Da Fonseca, R. E. Bittar, M. H. B. Carvalho, and M. Zugaib, “Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study,” American Journal of Obstetrics and Gynecology, vol. 188, no. 2, pp. 419–424, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. P. J. Meis, M. Klebanoff, E. Thom et al., “Prevention of recurrent preterm delivery by 17 α-hydroxyprogesterone caproate,” The New England Journal of Medicine, vol. 348, no. 24, pp. 2379–2385, 2003. View at Google Scholar
  46. P. J. Meis, M. Klebanoff, E. Thom et al., “Correction: Prevention of recurrent preterm delivery by 17 α-hydroxyprogesterone caproate,” The New England Journal of Medicine, vol. 349, no. 13, p. 1299, 2003. View at Publisher · View at Google Scholar
  47. E. B. Fonseca, E. Celik, M. Parra, M. Singh, K. H. Nicolaides, and Fetal Medicine Foundation Second Trimester Screening Group, “Progesterone and the risk of preterm birth among women with a short cervix,” The New England Journal of Medicine, vol. 357, no. 5, pp. 462–469, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. S. S. Hassan, R. Romero, D. Vidyadhari et al., “Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial,” Ultrasound in Obstetrics and Gynecology, vol. 38, no. 1, pp. 18–31, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. P. Rai, S. Rajaram, N. Goel, R. Ayalur Gopalakrishnan, R. Agarwal, and S. Mehta, “Oral micronized progesterone for prevention of preterm birth,” International Journal of Gynecology and Obstetrics, vol. 104, no. 1, pp. 40–43, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Owen, G. Hankins, J. D. Iams et al., “Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length,” American Journal of Obstetrics & Gynecology, vol. 201, no. 4, pp. 375.e1–375.e8, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. V. Berghella, T. J. Rafael, J. M. Szychowski, O. A. Rust, and J. Owen, “Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis,” Obstetrics and Gynecology, vol. 117, no. 3, pp. 663–671, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. V. Berghella and A. D. MacKeen, “Cervical length screening with ultrasound-indicated cerclage compared with history-indicated cerclage for prevention of preterm birth: a meta-analysis,” Obstetrics and Gynecology, vol. 118, no. 1, pp. 148–155, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Elovitz and Z. Wang, “Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise,” American Journal of Obstetrics and Gynecology, vol. 190, no. 3, pp. 693–701, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. M. A. Elovitz and C. Mrinalini, “Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation?” The American Journal of Obstetrics and Gynecology, vol. 193, no. 3, part 2, pp. 1149–1155, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. L. W. Doyle, C. A. Crowther, P. Middleton, S. Marret, and D. Rouse, “Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD004661, 2009. View at Publisher · View at Google Scholar
  56. American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine, “Committee Opinion No. 573: magnesium sulfate use in obstetrics,” Obstetrics and Gynecology, vol. 122, no. 3, pp. 727–728, 2013. View at Google Scholar
  57. C. T. J. van Velthoven, A. Kavelaars, F. van Bel, and C. J. Heijnen, “Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain,” Brain, Behavior, and Immunity, vol. 25, no. 7, pp. 1342–1348, 2011. View at Publisher · View at Google Scholar
  58. R. Berger and Y. Garnier, “Pathophysiology of perinatal brain damage,” Brain Research Reviews, vol. 30, no. 2, pp. 107–134, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. L. Nowak, P. Bregestovski, P. Ascher, A. Herbet, and A. Prochiantz, “Magnesium gates glutamate-activated channels in mouse central neurones,” Nature, vol. 307, no. 5950, pp. 462–465, 1984. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Hallak, J. W. Hotra, and W. J. Kupsky, “Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia,” Obstetrics and Gynecology, vol. 96, no. 1, pp. 124–128, 2000. View at Publisher · View at Google Scholar · View at Scopus
  61. A. G. Euser and M. J. Cipolla, “Magnesium sulfate for the treatment of eclampsia: a brief review,” Stroke, vol. 40, no. 4, pp. 1169–1175, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Faragó, C. Szabó, E. Dóra, I. Horváth, and A. G. B. Kovách, “Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations,” Journal of Cerebral Blood Flow and Metabolism, vol. 11, no. 1, pp. 161–164, 1991. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. Garnier, J. Middelanis, A. Jensen, and R. Berger, “Neuroprotective effects of magnesium on metabolic disturbances in fetal hippocampal slices after oxygen-glucose deprivation: mediation by nitric oxide system,” Journal of the Society for Gynecologic Investigation, vol. 9, no. 2, pp. 86–92, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. K. B. Nelson and J. K. Grether, “Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants?” Pediatrics, vol. 95, no. 2, pp. 263–269, 1995. View at Google Scholar · View at Scopus
  65. J. C. Hauth, R. L. Goldenberg, K. G. Nelson, M. B. DuBard, M. A. Peralta, and F. L. Gaudier, “Reduction of cerebral palsy with maternal MgSO4 treatment in newborns weighing 500–1000 g,” American Journal of Obstetrics & Gynecology, vol. 172, p. 419, 1995. View at Google Scholar
  66. D. E. Schendel, C. J. Berg, M. Yeargin-Allsopp, C. A. Boyle, and P. Decoufle, “Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years,” Journal of the American Medical Association, vol. 276, no. 22, pp. 1805–1810, 1996. View at Publisher · View at Google Scholar · View at Scopus
  67. T. E. Wiswell, L. J. Graziani, J. L. Caddell, N. Vecchione, C. Stanley, and A. R. Spitzer, “Maternally administered magnesium sulphate protects against early brain injury and long-term adverse neurodevelopmental outcomes in preterm infants: a prospective study,” Pediatric Research, vol. 39, p. 253, 1996. View at Publisher · View at Google Scholar
  68. Y. Matsuda, S. Kouno, Y. Hiroyama et al., “Intrauterine infection, magnesium sulfate exposure and cerebral palsy in infants born between 26 and 30 weeks of gestation,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 91, no. 2, pp. 159–164, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Paneth, J. Jetton, J. Pinto-Martin, and M. Susser, “Magnesium sulfate in labor and risk of neonatal brain lesions and cerebral palsy in low birth weight infants. The Neonatal Brain Hemorrhage Study Analysis Group,” Pediatrics, vol. 99, no. 5, p. E1, 1997. View at Google Scholar · View at Scopus
  70. T. M. O'Shea, K. L. Klinepeter, and R. G. Dillard, “Prenatal events and the risk of cerebral palsy in very low birth weight infants,” American Journal of Epidemiology, vol. 147, no. 4, pp. 362–369, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. D. Wilson-Costello, E. Borawski, H. Friedman, R. Redline, A. A. Fanaroff, and M. Hack, “Perinatal correlates of cerebral palsy and other neurologic impairment among very low birth weight children,” Pediatrics, vol. 102, no. 2, pp. 315–322, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. C. A. Boyle, M. Yeargin-Allsopp, D. E. Schendel, P. Holmgreen, and G. P. Oakley, “Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams,” American Journal of Epidemiology, vol. 152, no. 2, pp. 120–124, 2000. View at Publisher · View at Google Scholar · View at Scopus
  73. J. K. Grether, J. Hoogstrate, E. Walsh-Greene, and K. B. Nelson, “Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia,” American Journal of Obstetrics and Gynecology, vol. 183, no. 3, pp. 717–725, 2000. View at Publisher · View at Google Scholar · View at Scopus
  74. M. M. Costantine, H. Y. How, K. Coppage, R. A. Maxwell, and B. M. Sibai, “Does peripartum infection increase the incidence of cerebral palsy in extremely low birthweight infants?” American Journal of Obstetrics and Gynecology, vol. 196, no. 5, pp. e8–e8, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. R. Mittendorf, J. Dambrosia, P. G. Pryde et al., “Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants,” The American Journal of Obstetrics and Gynecology, vol. 186, no. 6, pp. 1111–1118, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. C. A. Crowther, J. E. Hiller, L. W. Doyle, R. R. Haslam, and Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative Group, “Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial,” The Journal of the American Medical Association, vol. 290, no. 20, pp. 2669–2676, 2003. View at Publisher · View at Google Scholar
  77. Magpie Trial Follow-Up Study Collaborative Group, “The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 114, no. 3, pp. 289–299, 2007. View at Publisher · View at Google Scholar
  78. S. Marret, L. Marpeau, C. Follet-Bouhamed et al., “Effect of magnesium sulphate on mortality and neurologic morbidity of the very-preterm newborn with two-year neurological outcome: results of the prospective PREMAG trial,” Gynecologie Obstetrique Fertilite, vol. 36, no. 3, pp. 278–288, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. D. J. Rouse, D. G. Hirtz, and E. Thom, “Eunice kennedy shriver NICHD maternal-fetal medicine units network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy,” The New England Journal of Medicine, vol. 359, no. 9, pp. 895–905, 2008. View at Publisher · View at Google Scholar
  80. L. W. Doyle, P. J. Anderson, R. Haslam, K. J. Lee, C. Crowther, and Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Study Group, “School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo,” The Journal of the American Medical Association, vol. 312, no. 11, pp. 1105–1113, 2014. View at Publisher · View at Google Scholar
  81. A. Conde-Agudelo and R. Romero, “Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis,” American Journal of Obstetrics & Gynecology, vol. 200, no. 6, pp. 595–609, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. A. G. Cahill and A. B. Caughey, “Magnesium for neuroprophylaxis: fact or fiction?” The American Journal of Obstetrics and Gynecology, vol. 200, no. 6, pp. 590–594, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. R. Mittendorf, J. Dambrosia, P. G. Pryde et al., “Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants,” American Journal of Obstetrics and Gynecology, vol. 186, no. 6, pp. 1111–1118, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. L. L. Ow, A. Kennedy, E. A. McCarthy, and S. P. Walker, “Feasibility of implementing magnesium sulphate for neuroprotection in a tertiary obstetric unit,” Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 52, no. 4, pp. 356–360, 2012. View at Publisher · View at Google Scholar
  85. “X4PB. Prädiktion und Prävention der Frühgeb urt,” Der Frauenarzt, vol. 54, pp. 1060–1071, 2013.
  86. A. C. Yao and J. Lind, “Blood flow in the umbilical vessels during the third stage of labor,” Biology of the Neonate, vol. 25, no. 3-4, pp. 186–193, 1974. View at Publisher · View at Google Scholar · View at Scopus
  87. G. J. Hofmeyr, K. D. Bolton, D. C. Bowen, and J. J. Govan, “Periventricular/intraventricular haemorrhage and umbilical cord clampings. Findings and hypothesis,” South African Medical Journal, vol. 73, no. 2, pp. 104–106, 1988. View at Google Scholar · View at Scopus
  88. O. Baenziger, F. Stolkin, M. Keel et al., “The influence of the timing of cord clamping on postnatal cerebral oxygenation in preterm neonates: a randomized, controlled trial,” Pediatrics, vol. 119, no. 3, pp. 455–459, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Bonnar, G. P. McNicol, and A. S. Douglas, “The blood coagulation and fibrinolytic systems the newborn and the mother at birth,” Journal of Obstetrics and Gynaecology of the British Commonwealth, vol. 78, no. 4, pp. 355–360, 1971. View at Publisher · View at Google Scholar · View at Scopus
  90. D.-H. Park, C. V. Borlongan, A. E. Willing et al., “Human umbilical cord blood cell grafts for brain ischemia,” Cell Transplantation, vol. 18, no. 9, pp. 985–998, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. H. Rabe, A. Wacker, G. Hülskamp et al., “A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants,” European Journal of Pediatrics, vol. 159, no. 10, pp. 775–777, 2000. View at Publisher · View at Google Scholar · View at Scopus
  92. M. McDonnell and D. J. Henderson-Smart, “Delayed umbilical cord clamping in preterm infants: a feasibility study,” Journal of Paediatrics and Child Health, vol. 33, no. 4, pp. 308–310, 1997. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Kinmond, T. C. Aitchison, B. M. Holland, J. G. Jones, T. L. Turner, and C. A. J. Wardrop, “Umbilical cord clamping and preterm infants: a randomised trial,” British Medical Journal, vol. 306, no. 6871, pp. 172–175, 1993. View at Google Scholar · View at Scopus
  94. J. S. Mercer, B. R. Vohr, M. M. McGrath, J. F. Padbury, M. Wallach, and W. Oh, “Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial,” Pediatrics, vol. 117, no. 4, pp. 1235–1242, 2006. View at Google Scholar
  95. American College of Obstetricians and Gynecologists, “Committee Opinion No.543: timing of umbilical cord clamping after birth,” Obstetrics & Gynecology, vol. 120, no. 6, pp. 1522–1526, 2012. View at Publisher · View at Google Scholar
  96. H. Rabe, A. Jewison, R. Fernandez Alvarez et al., “Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial,” Obstetrics and Gynecology, vol. 117, no. 2, pp. 205–211, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. L. Bennet, V. Roelfsema, P. Pathipati, J. S. Quaedackers, and A. J. Gunn, “Relationship between evolving epileptiform activity and delayed loss of mitochondrial activity after asphyxia measured by near-infrared spectroscopy in preterm fetal sheep,” Journal of Physiology, vol. 572, no. 1, pp. 141–154, 2006. View at Publisher · View at Google Scholar · View at Scopus
  98. A. J. Gunn, T. R. Gunn, H. H. de Haan, C. E. Williams, and P. D. Gluckman, “Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs,” The Journal of Clinical Investigation, vol. 99, no. 2, pp. 248–256, 1997. View at Publisher · View at Google Scholar · View at Scopus
  99. E. C. Jensen, L. Bennet, C. J. Hunter, G. C. Power, and A. J. Gunn, “Post-hypoxic hypoperfusion is associated with suppression of cerebral metabolism and increased tissue oxygenation in near-term fetal sheep,” Journal of Physiology, vol. 572, no. 1, pp. 131–139, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Lorek, Y. Takei, E. B. Cady et al., “Delayed ('secondary') cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy,” Pediatric Research, vol. 36, no. 6, pp. 699–706, 1994. View at Publisher · View at Google Scholar · View at Scopus
  101. S. C. Roth, J. Baudin, E. Cady et al., “Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years,” Developmental Medicine and Child Neurology, vol. 39, no. 11, pp. 718–725, 1997. View at Google Scholar · View at Scopus
  102. F. Colbourne and D. Corbett, “Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection,” Journal of Neuroscience, vol. 15, no. 11, pp. 7250–7260, 1995. View at Google Scholar · View at Scopus
  103. R. Geddes, R. C. Vannucci, and S. J. Vannucci, “Delayed cerebral atrophy following moderate hypoxia-ischemia in the immature rat,” Developmental Neuroscience, vol. 23, no. 3, pp. 180–185, 2001. View at Publisher · View at Google Scholar · View at Scopus
  104. B. S. Stone, J. Zhang, D. W. Mack, S. Mori, L. J. Martin, and F. J. Northington, “Delayed neural network degeneration after neonatal hypoxia-ischemia,” Annals of Neurology, vol. 64, no. 5, pp. 535–546, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. R. D. Barrett, L. Bennet, J. Davidson et al., “Destruction and reconstruction: hypoxia and the developing brain,” Birth Defects Research Part C: Embryo Today: Reviews, vol. 81, no. 3, pp. 163–176, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. A. J. Friedenstein, R. K. Chailakhyan, N. V. Latsinik, A. F. Panasyuk, and I. V. Keiliss-Borok, “Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo,” Transplantation, vol. 17, no. 4, pp. 331–340, 1974. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Najar, G. Raicevic, H. I. Boufker et al., “Adipose-tissue-derived and Wharton's jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor,” Tissue Engineering Part A, vol. 16, no. 11, pp. 3537–3546, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Yust-Katz, Y. Fisher-Shoval, Y. Barhum et al., “Placental mesenchymal stromal cells induced into neurotrophic factor-producing cells protect neuronal cells from hypoxia and oxidative stress,” Cytotherapy, vol. 14, no. 1, pp. 45–55, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. C. Meier, J. Middelanis, B. Wasielewski et al., “Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells,” Pediatric Research, vol. 59, no. 2, pp. 244–249, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. C. T. J. van Velthoven, A. Kavelaars, F. van Bel, and C. J. Heijnen, “Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration,” Brain, Behavior, and Immunity, vol. 24, no. 3, pp. 387–393, 2010. View at Publisher · View at Google Scholar · View at Scopus
  111. J. A. Lee, B. I. Kim, C. H. Jo et al., “Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in neonatal rat model,” Pediatric Research, vol. 67, no. 1, pp. 42–46, 2010. View at Publisher · View at Google Scholar
  112. R. K. Jellema, T. G. A. M. Wolfs, V. Lima Passos et al., “Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia,” PLoS ONE, vol. 8, no. 8, Article ID e73031, 2013. View at Publisher · View at Google Scholar · View at Scopus
  113. C. T. J. van Velthoven, A. Kavelaars, and C. J. Heijnen, “Mesenchymal stem cells as a treatment for neonatal ischemic brain damage,” Pediatric Research, vol. 71, no. 4, part 2, pp. 474–481, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. C. T. J. vn Velthoven, A. Kavelaars, F. van Bel, and C. J. Heijnen, “Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain,” Brain, Behavior, and Immunity, vol. 25, no. 7, pp. 1342–1348, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Gritti, P. Frölichsthal-Schoeller, R. Galli et al., “Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain,” The Journal of Neuroscience, vol. 19, no. 9, pp. 3287–3297, 1999. View at Google Scholar · View at Scopus
  116. B. A. Reynolds and S. Weiss, “Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system,” Science, vol. 255, no. 5052, pp. 1707–1710, 1992. View at Publisher · View at Google Scholar · View at Scopus
  117. T. Kobayashi, H. Ahlenius, P. Thored, R. Kobayashi, Z. Kokaia, and O. Lindvall, “Intracerebral infusion of glial cell line-derived neurotrophic factor promotes striatal neurogenesis after stroke in adult rats,” Stroke, vol. 37, no. 9, pp. 2361–2367, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. L. H. Shen, Y. Li, and M. Chopp, “Astrocytic endogenous glial cell derived neurotrophic factor production is enhanced by bone marrow stromal cell transplantation in the ischemic boundary zone after stroke in adult rats,” GLIA, vol. 58, no. 9, pp. 1074–1081, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. K. Lai, B. K. Kaspar, F. H. Gage, and D. V. Schaffer, “Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo,” Nature Neuroscience, vol. 6, no. 1, pp. 21–27, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. K. Lai, B. K. Kaspar, F. H. Gage, and D. V. Schaffer, “Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo,” Nature Neuroscience, vol. 6, pp. 21–27, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. R. J. Felling, M. J. Snyder, M. J. Romanko et al., “Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia,” The Journal of Neuroscience, vol. 26, no. 16, pp. 4359–4369, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. S. T. Carmichael, “Cellular and molecular mechanisms of neural repair after stroke: making waves,” Annals of Neurology, vol. 59, no. 5, pp. 735–742, 2006. View at Publisher · View at Google Scholar · View at Scopus
  123. F. J. Rivera, M. Kandasamy, S. Couillard-Despres et al., “Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors,” Journal of Neurochemistry, vol. 107, no. 3, pp. 832–843, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. C. T. J. van Velthoven, A. Kavelaars, F. van Bel, and C. J. Heijnen, “Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function,” The Journal of Neuroscience, vol. 30, no. 28, pp. 9603–9611, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. Y. Li, J. Chen, C. L. Zhang et al., “Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells,” GLIA, vol. 49, no. 3, pp. 407–417, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. L. H. Shen, Y. Li, Q. Gao, S. Savant-Bhonsale, and M. Chopp, “Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain,” GLIA, vol. 56, no. 16, pp. 1747–1754, 2008. View at Publisher · View at Google Scholar · View at Scopus
  127. C. T. Ekdahl, Z. Kokaia, and O. Lindvall, “Brain inflammation and adult neurogenesis: the dual role of microglia,” Neuroscience, vol. 158, no. 3, pp. 1021–1029, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. M. Czeh, P. Gressens, and A. M. Kaindl, “The yin and yang of microglia,” Developmental Neuroscience, vol. 33, no. 3-4, pp. 199–209, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. U.-K. Hanisch and H. Kettenmann, “Microglia: active sensor and versatile effector cells in the normal and pathologic brain,” Nature Neuroscience, vol. 10, no. 11, pp. 1387–1394, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Schwartz, O. Butovsky, W. Brück, and U.-K. Hanisch, “Microglial phenotype: is the commitment reversible?” Trends in Neurosciences, vol. 29, no. 2, pp. 68–74, 2006. View at Publisher · View at Google Scholar · View at Scopus
  131. J. Aarum, K. Sandberg, S. L. B. Haeberlein, and M. A. A. Persson, “Migration and differentiation of neural precursor cells can be directed by microglia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15983–15988, 2003. View at Publisher · View at Google Scholar · View at Scopus
  132. P. Thored, U. Heldmann, W. Gomes-Leal et al., “Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke,” GLIA, vol. 57, no. 8, pp. 835–849, 2009. View at Publisher · View at Google Scholar · View at Scopus
  133. R. C. Lai, F. Arslan, M. M. Lee et al., “Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury,” Stem Cell Research, vol. 4, no. 3, pp. 214–222, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. P. J. Shughrue, M. V. Lane, and I. Merchenthaler, “Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system,” The Journal of Comparative Neurology, vol. 388, no. 4, pp. 507–525, 1997. View at Google Scholar
  135. N. Laflamme, R. E. Nappi, G. Drolet, C. Labrie, and S. Rivest, “Expression and neuropeptidergic characterization of estrogen receptors (ERα and ERβ) throughout the rat brain: anatomical evidence of distinct roles of each subtype,” Journal of Neurobiology, vol. 36, no. 3, pp. 357–378, 1998. View at Publisher · View at Google Scholar
  136. A. E. Clipperton-Allen, A. W. Lee, A. Reyes et al., “Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice,” Physiology & Behavior, vol. 105, no. 4, pp. 915–924, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. D. G. Zuloaga, S. L. Yahn, Y. Pang et al., “Distribution and estrogen regulation of membrane progesterone receptor-β in the female rat brain,” Endocrinology, vol. 153, no. 9, pp. 4432–4443, 2012. View at Publisher · View at Google Scholar · View at Scopus
  138. S. Haraguchi, K. Sasahara, H. Shikimi, S.-I. Honda, N. Harada, and K. Tsutsui, “Estradiol promotes purkinje dendritic growth, spinogenesis, and synaptogenesis during neonatal life by inducing the expression of BDNF,” Cerebellum, vol. 11, no. 2, pp. 416–417, 2012. View at Publisher · View at Google Scholar · View at Scopus
  139. D. Tulchinsky, C. J. Hobel, E. Yeager, and J. R. Marshall, “Plasma estradiol, estriol, and progesterone in human pregnancy. II. Clinical applications in Rh-isoimmunization disease,” The American Journal of Obstetrics and Gynecology, vol. 113, no. 6, pp. 766–770, 1972. View at Google Scholar · View at Scopus
  140. C. E. Wood, “Estrogen/hypothalamus-pituitary-adrenal axis interactions in the fetus: the interplay between placenta and fetal brain,” Journal of the Society for Gynecologic Investigation, vol. 12, no. 2, pp. 67–76, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Nuñez, Z. Yang, Y. Jiang, T. Grandys, I. Mark, and S. W. Levison, “17β-Estradiol protects the neonatal brain from hypoxia-ischemia,” Experimental Neurology, vol. 208, no. 2, pp. 269–276, 2007. View at Publisher · View at Google Scholar · View at Scopus
  142. B. Gerstner, J. Lee, T. M. DeSilva, F. E. Jensen, J. J. Volpe, and P. A. Rosenberg, “17β-estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain,” Journal of Neuroscience Research, vol. 87, no. 9, pp. 2078–2086, 2009. View at Publisher · View at Google Scholar · View at Scopus
  143. M. M. Müller, J. Middelanis, C. Meier, D. Surbek, and R. Berger, “17β-estradiol protects 7-day old rats from acute brain injury and reduces the number of apoptotic cells,” Reproductive Sciences, vol. 20, no. 3, pp. 253–261, 2013. View at Publisher · View at Google Scholar · View at Scopus
  144. E. R. Deutsch, T. R. Espinoza, F. Atif, E. Woodall, J. Kaylor, and D. W. Wright, “Progesterone's role in neuroprotection, a review of the evidence,” Brain Research, vol. 1530, pp. 82–105, 2013. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Trotter, L. Maier, and F. Pohlandt, “Management of the extremely preterm infant: is the replacement of estradiol and progesterone beneficial?” Paediatric Drugs, vol. 3, no. 9, pp. 629–637, 2001. View at Publisher · View at Google Scholar · View at Scopus
  146. R. Hunt, P. G. Davis, and T. Inder, “Replacement of estrogens and progestins to prevent morbidity and mortality in preterm infants,” The Cochrane Database of Systematic Reviews, no. 4, Article ID CD003848, 2004. View at Google Scholar · View at Scopus
  147. C. Behl and F. Holsboer, “The female sex hormone oestrogen as a neuroprotectant,” Trends in Pharmacological Sciences, vol. 20, no. 11, pp. 441–444, 1999. View at Publisher · View at Google Scholar · View at Scopus
  148. C. Behl, “Oestrogen as a neuroprotective hormone,” Nature Reviews Neuroscience, vol. 3, no. 6, pp. 433–442, 2002. View at Google Scholar · View at Scopus
  149. S. J. Lee and B. S. McEwen, “Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications,” Annual Review of Pharmacology and Toxicology, vol. 41, pp. 569–591, 2001. View at Publisher · View at Google Scholar · View at Scopus
  150. R. J. Bicknell, “Sex-steroid actions on neurotransmission,” Current Opinion in Neurology, vol. 11, no. 6, pp. 667–671, 1998. View at Publisher · View at Google Scholar · View at Scopus
  151. Q. Gu, K. S. Korach, and R. L. Moss, “Rapid action of 17β-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors,” Endocrinology, vol. 140, no. 2, pp. 660–666, 1999. View at Publisher · View at Google Scholar · View at Scopus
  152. G. G. J. M. Kuiper, B. Carlsson, K. Grandien et al., “Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors and alpha and beta,” Endocrinology, vol. 138, no. 3, pp. 863–870, 1997. View at Publisher · View at Google Scholar · View at Scopus
  153. S. M. Hyder, C. Chiappetta, and G. M. Stancel, “Interaction of human estrogen receptors α and β with the same naturally occurring estrogen response elements,” Biochemical Pharmacology, vol. 57, no. 6, pp. 597–601, 1999. View at Publisher · View at Google Scholar · View at Scopus
  154. S. Kahlert, S. Nuedling, M. van Eickels, H. Vetter, R. Meyer, and C. Grohé, “Estrogen receptor a rapidly activates the IGF-1 receptor pathway,” The Journal of Biological Chemistry, vol. 275, no. 24, pp. 18447–18453, 2000. View at Publisher · View at Google Scholar · View at Scopus
  155. K. G. Brywe, C. Mallard, M. Gustavsson et al., “IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement of Akt and GSK3β?” European Journal of Neuroscience, vol. 21, no. 6, pp. 1489–1502, 2005. View at Publisher · View at Google Scholar · View at Scopus
  156. Y. Zhang, O. Tounekti, B. Akerman, C. G. Goodyer, and A. LeBlanc, “17-beta-estradiol induces an inhibitor of active caspases,” The Journal of Neuroscience, vol. 21, no. 20, article RC176, 2001. View at Google Scholar
  157. T. Ishrat, I. Sayeed, F. Atif, F. Hua, and D. G. Stein, “Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases,” Experimental Neurology, vol. 226, no. 1, pp. 183–190, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. C.-Y. Xu, S. Li, X.-Q. Li, and D.-L. Li, “Effect of progesterone on MMP-3 expression in neonatal rat brain after hypoxic-ischemia,” Zhongguo Ying Yong Sheng Li Xue Za Zhi, vol. 26, no. 3, pp. 370–373, 2010. View at Google Scholar · View at Scopus
  159. T. Ishrat, I. Sayeed, F. Atif, F. Hua, and D. G. Stein, “Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase/protein kinase B signaling pathway,” Neuroscience, vol. 210, pp. 442–450, 2012. View at Publisher · View at Google Scholar · View at Scopus
  160. C. L. Gibson, D. Constantin, M. J. W. Prior, P. M. W. Bath, and S. P. Murphy, “Progesterone suppresses the inflammatory response and nitric oxide synthase-2 expression following cerebral ischemia,” Experimental Neurology, vol. 193, no. 2, pp. 522–530, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. C. Jiang, K. Cui, J. Wang, and Y. He, “Microglia and cyclooxygenase-2: possible therapeutic targets of progesterone for stroke,” International Immunopharmacology, vol. 11, no. 11, pp. 1925–1931, 2011. View at Publisher · View at Google Scholar
  162. J. Wang, Y. Zhao, C. Liu, C. Jiang, C. Zhao, and Z. Zhu, “Progesterone inhibits inflammatory response pathways after permanent middle cerebral artery occlusion in rats,” Molecular Medicine Reports, vol. 4, no. 2, pp. 319–324, 2011. View at Publisher · View at Google Scholar
  163. T. Coughlan, C. Gibson, and S. Murphy, “Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro,” Journal of Neurochemistry, vol. 93, no. 4, pp. 932–942, 2005. View at Publisher · View at Google Scholar · View at Scopus
  164. R. Aggarwal, B. Medhi, A. Pathak, V. Dhawan, and A. Chakrabarti, “Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice,” Journal of Pharmacy and Pharmacology, vol. 60, no. 6, pp. 731–737, 2013. View at Publisher · View at Google Scholar · View at Scopus
  165. Y. Zhao, J. Wang, C. Liu, C. Jiang, C. Zhao, and Z. Zhu, “Progesterone influences postischemic synaptogenesis in the CA1 region of the hippocampus in rats,” Synapse, vol. 65, no. 9, pp. 880–891, 2011. View at Publisher · View at Google Scholar · View at Scopus
  166. M. Tsuji, A. Taguchi, M. Ohshima, Y. Kasahara, and T. Ikeda, “Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats,” Experimental Neurology, vol. 233, no. 1, pp. 214–220, 2012. View at Publisher · View at Google Scholar · View at Scopus