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Maternal and Perinatal Care(Cooperating field)Maternal and Perinatal Care

Introduction

The Center for Maternal-Neonatal Care has 12 beds in NICU and 24 beds in GCU as the division of neonatology. The unit takes care of infants with very low birth weight infants, newborn infants with neonatal diseases (asphyxia, respiratory disorder, surgical complications, etc.). Strong fields in the unit are congenital diaphragmatic hernia, severe asphyxia neonatorum/severe hypoxic-ischemic encephalopathy, severe fetal growth retardation/small for gestational age infants, almost all kinds of congenital surgical complications, and congenital malformations. The unit has approximately 300 admissions in NICU/GCU including 15 ELBW babies and 30 congenital malformations per year.

Research Projects

1) Stem cell therapies for perinatal brain injuries
Many newborns suffer badly from hypoxia-ischemia (HI). Perinatal HI leads to millions of neonatal deaths and neurological disadvantages. However, no effective treatments have been established against brain damage induced by HI except brain hypothermia, although even this is not effective for severe HI. Therefore, it is urgent to develop a novel therapy against HI.
Cell transplantation therapies, including the use of embryonic stem cells, neural stem/progenitor cells (NSPC), bone marrow stromal cells and umbilical cord blood cells, may represent a novel treatment for HI.
We have been studying with neonatal HI model rats and cultured cells to develop novel therapies for perinatal HI. We showed that transplantation of fetal NSPC together with chondroitinase ABC (ChABC) into the ventricle significantly reduce infarction after HI injury (Sato Y, et al. Reprod Sci, 2008, Sato Y, et al. Curr Stem Cell Res Ther, 2009).
As using cells from fetuses can bring ethical problems for us, and injection into brain is invasive, currently, we are focusing on bone marrow stromal cells and umbilical cord blood cells as sources of stem cells, which are readily available, so many ethical considerations can be avoided. We have shown that umbilical cord blood cells can reduce HI injury with rat model (Hattori T, et al. Dev Neurosci, 2015; 37: 95-104).and started a Phase 1 clinical study.

2) Neurological disabilities in fetal growth restriction infants (FGR)
FGR infants develop mental retardation and/or cognitive deficit in later life, but the mechanism underlying these disabilities has not been elucidated, and postnatal aggressive nutrition is only one strategy at this moment.
We have already established an FGR model rat induced by continuous administration of a synthetic thromboxane A(2) analogue (STA(2)) to pregnant rats (Hayakawa M, et al. J. Soc. Gynecol. Investig. 2006). With this model, we have shown that volume of cortical neuron is significantly reduced in FGR brains (Hayakawa M, et al. Early Hum Dev, 1999), neuronal migration is delayed in FGR brains in the early neonatal period, expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are decreased (Fukami E, et al. Early Hum Dev, 2000), FGR infants have less number of neurons and more apoptotic cells in cortical plate, and exhibit learning deficit (Saito A, et al. Exp Neurol, 2009), and that lactate and pyruvate levels were reduced significantly, glucose content tended to be increased, and glycogen content tended to be lower in the brain of FGR rats (Hayakawa M, et al. Pediatr Res, 2011).

3) Novel pharmacologic treatments for perinatal brain injuries
Glutamate excitotoxicity has been reported to be pathologically linked to many neuronal diseases including perinatal HI. We have shown that a highly sulfated CS preparation, CS-E, exerts a neuroprotective effect on neurons treated with various glutamate analogs (Sato Y, et al. J. Neurochem., 2008).
We have been also investigating whether some other substances/medicines have a neuroprotective effect with both the animal model and cultured cells.

4) Effects of various medicines used in neonatal intensive care unit (NICU) on immature brains
There are not a few medicines we use in NICU, but the effects of them on the immature brains are not largely unknown. We have been investigating the effects both in vitro and in vivo. Currently, we are studying about various steroids and methylxanthines. We have shown that dexamethasone administration to the neonatal rat results in neurological dysfunction at the juvenile stage even at low doses(Ichinohashi Y, et al. Early Hum Dev, 2013).

Faculty Members

FacultyPositionDepartment
Masahiro Hayakawa Clinical Professor Division of Neonatology, Center for Maternal-Neonatal Care
Yoshiaki Sato Associate Professor Division of Neonatology, Center for Maternal-Neonatal Care
Yukako Muramatsu Assistant Professor Center for Postgraduate Clinical Training and Career Development
Akiko Saito Assistant Professor Division of Neonatology, Center for Maternal-Neonatal Care
Miharu Ito Assistant Professor Division of Neonatology, Center for Maternal-Neonatal Care
Yuichiro Sugiyama Assistant Professor Division of Neonatology, Center for Maternal-Neonatal Care
Takashi Tachibana Assistant Professor Division of Neonatology, Center for Maternal-Neonatal Care
Yuma Kitase Division of Neonatology, Center for Maternal-Neonatal Care
Haruka Mimatsu Division of Neonatology, Center for Maternal-Neonatal Care
Kazuto Ueda Division of Neonatology, Center for Maternal-Neonatal Care
Ryo Tanaka Division of Neonatology, Center for Maternal-Neonatal Care

Bibliography

  • 2016
    1. Muramatsu Y, Tokita Y, Mizuno S, Nakamura M. Disparities in visuo-spatial constructive abilities in Williams syndrome patients with typical deletion on chromosome 7q11.23. Brain Dev, in press
    2. Ohshima M, Taguchi A, Sato Y, Ogawa Y, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T, Tsuji M. Evaluations of intravenous administration of CD34+ human umbilical cord blood cells in a mouse model of neonatal hypoxic-ischemic encephalopathy. Dev Neurosci, 2016 in press.
    3. Ohshima M, Coq J, Otani K, Hattori Y, Ogawa Y, Sato Y, Harada-Shiba M, Ihara M, Tsuji M. Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity. Sci Rep, 2016 in press.
    4. Kawashima N, Kawada J, Nishikado Y, Kitase Y, Ito S, Muramatsu H, Sato Y, Kato T, Natsume J, Kojima S. Abnormal urinalysis on day 7 in patients with IgA vasculitis (Henoch–Schönlein purpura). Nagoya J. Med. Sci., 2016 in press.
    5. Hattori T, Hayakawa M, Ito M, Sato Y, K. T, Kanamori Y, Okuyama H, Inamura N, Takahashi S, Fujino Y, Taguchi T, Usui N. The relationship between three sings of fetal magnetic resonance imaging and severity of congenital diaphragmatic hernia. J Perinatol, 2016 in press.
    6. Muramatsu Y, Ito M, Oshima T, Kojima S, Ohno K. Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats. Pediatr Pulmonol, 2016; 51(9): 928-35.
  • 2015
    1. Sato Y, Oshiro M, Takemoto K, Hosono H, Saito A, Kondo T, Aizu K, Matsusawa M, Futamura Y, Asami T, Terasaki H, Hayakawa M. Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity. J Perinatol, 2015; 35: 965-969.
    2. Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev, 2015; 37: 376-386.
    3. Nakano T, Kotani T, Mano Y, Tsuda H, Imai K, Ushida T, Li H, Miki R, Sumigama S, Sato Y, Iwase A, Hirakawa A, Asai M, Toyokuni S, Kikkawa F. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J Clin Biochem Nutr, 2015; 57: 178-182.
    4. Hattori Y, Kotani T, Tsuda H, Mano Y, Tu L, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S, Kikkawa F. Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. Free Radic Res, 2015; 49: 1026-1037.
    5. Hattori T, Sato Y, Kondo T, Ichinohashi Y, Sugiyama Y, Yamamoto M, Kotani T, Hirata H, Hirakawa A, Suzuki S, Tsuji M, Ikeda T, Nakanishi K, Kojima S, Blomgren K, Hayakawa M. Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats. Dev Neurosci, 2015; 37: 95-104.
    6. Futamura Y, Asami T, Nonobe N, Kachi S, Ito Y, Sato Y, Hayakawa M, Terasaki H. Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes. Jpn J Ophthalmol, 2015; 59: 378-388.
  • 2014
    1. Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T. Effects of intravenous administration of umbilical cord blood CD34 cells in a mouse model of neonatal stroke. Neuroscience, 2014; 263C: 148-158.
    2. Tsuda H, Kotani T, Sumigama S, Mano Y, Hua L, Hayakawa H, Hayakawa M, Sato Y, Kikkawa F. Effect of placenta previa on neonatal respiratory disorders and amniotic lamellar body counts at 36-38weeks of gestation. Early Hum Dev, 2014; 90: 51-54.
    3. Ito M, Kidokoro H, Sugiyama Y, Sato Y, Natsume J, Watanabe K, Hayakawa M. Paradoxical downward seizure pattern on amplitude-integrated electroencephalogram. J Perinatol, 2014; 34: 642-644.
  • 2013
    1. Hirai M, Muramatsu Y, Mizuno S, Kurahashi N, Kurahashi H, Nakamura M. Developmental changes in mental rotation ability and visual perspective-taking in children and adults with Williams syndrome. Front Hum Neurosci, 2013; 7: 856.
    2. Suzumori N, Kaname T, Muramatsu Y, Yanagi K, Kumagai K, Mizuno S, Naritomi K, Saitoh S, Sugiura-Ogasawara M. Prenatal diagnosis of X-linked recessive Lenz microphthalmia syndrome. J Obstet Gynaecol Res, 2013; 39(11): 1545-7.
    3. Watanabe Y, Tsuda H, Kotani T, Sumigama S, Mano Y, Hayakawa M, Sato Y, Kikkawa F. Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model. Pediatr Res, 2013; 73: 344-348.
    4. Sato Y, Shinjyo N, Sato M, Osato K, Zhu C, Pekna M, Kuhn HG, Blomgren K. Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer. Cell Death Dis, 2013; 4: e591.
    5. Sato Y, Kawataki M, Hirakawa A, Toyoshima K, Kato T, Itani Y, Hayakawa M. The diameter of the inferior vena cava provides a noninvasive way of calculating central venous pressure in neonates. Acta Paediatr, 2013; 102: e241-246.
    6. Ichinohashi Y, Sato Y, Saito A, Ito M, Watanabe K, Hayakawa M, Nakanishi K, Wakatsuki A, Oohira A. Dexamethasone administration to the neonatal rat results in neurological dysfunction at the juvenile stage even at low doses. Early Hum Dev, 2013; 89: 283-288.
    7. Ibi D, Nagai T, Nakajima A, Mizoguchi H, Kawase T, Tsuboi D, Kano S, Sato Y, Hayakawa M, Lange UC, Adams DJ, Surani MA, Satoh T, Sawa A, Kaibuchi K, Nabeshima T, Yamada K. Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice. Glia, 2013; 61: 679-693.
  • 2012
    1. Nakanishi K, Ito M, Sato Y, Oohira A. A highly-sulfated chondroitin sulfate, CS-E, adsorbs specifically to neurons with nuclear condensation. Neurosci Res, 2012; 74: 223-229.
    2. Ismael O, Shimada A, Hama A, Takahashi Y, Sato Y, Hayakawa M, Tsuchiya H, Tainaka T, Ono Y, Kaneko K, Ando H, Sato K, Kojima S. Congenital pancreatoblastoma associated with beta-catenin mutation. Pediatr Blood Cancer, 2012; 58: 827.
  • 2011
    1. Hayakawa M, Sato Y, Hattori T, Ichinohashi Y, Nakayama A, Yamamoto H, Hemmi H, Ito M, Ieda K, Kojima S. Carbohydrate and energy metabolism in the brain of rats with thromboxane A2-induced fetal growth restriction. Pediatr Res, 2011; 70: 21-24.
  • 2010
    1. Muramatsu Y, Kosho T, Magota M, Yokotsuka T, Ito M, Yasuda A, Kito O, Suzuki C, Nagata Y, Kawai S, Ikoma M, Hatano T, Nakayama M, Wakui K, Morisaki H, Morisaki T, FukushimaY. Progressive Aortic Root and Pulmonary Artery Aneurysms in a Neonate with Loeys-Dietz Syndrome, Type 1B. Am J Med Genet A, 2010; 152A(2): 417-21.
    2. Tagaya M, Sato Y, Hayakawa M. The diffusion weighted imaging for an early diagnosis of parasagittal injury. Pediatr Int., 2010; 52: 298-301.
    3. Osato K, Sato Y, Ochiishi T, Osato A, Zhu C, Sato M, Swanpalmer J, Modjtahedi N, Kroemer G, Kuhn HG, Blomgren K. Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation. Cell Death Dis, 2010; 1: e84.
    4. Nakanishi K, Sato Y, Oohira A. Biological activities of highly sulfated chondroitin sulfate polysaccharides on neural cells. Research Advances in Neurochemistry, Global Research Network, 2010: 1-10.
  • 2009
    1. Takemoto K, Nakayama A, Ito M, Sato Y, Saito A, Tori Y, Kaneko K, Ando H, Hayakawa M. Male gender is related to the development of parenteral nutrition-associated cholestasis in neonates. Journal of Neonatal-Perinatal Medicine, 2009; 2: 247–251.
    2. Sato Y, Oohira A. Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification. Curr Stem Cell Res Ther, 2009; 4: 200-209.
    3. Saito A, Matsui F, Hayashi K, Watanabe K, Ichinohashi Y, Sato Y, Hayakawa M, Kojima S, Oohira A. Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans. Exp Neurol, 2009; 219: 81-92.
  • 2008
    1. Sato Y, Nakanishi K, Tokita Y, Kakizawa H, Ida M, Maeda H, Matsui F, Aono S, Saito A, Kuroda Y, Hayakawa M, Kojima S, Oohira A. A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death. J. Neurochem., 2008; 104: 1565-1576.
    2. Sato Y, Nakanishi K, Hayakawa M, Kakizawa H, Saito A, Kuroda Y, Ida M, Tokita Y, Aono S, Matsui F, Kojima S, Oohira A. Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reprod Sci, 2008; 15: 613-620.
    3. Sato Y, Hayakawa M, Iwata O, Okumura A, Kato T, Hayakawa F, Kubota T, Maruyama K, Hasegawa M, Sato M, Oshiro M, Kito O, Kojima S. Delayed neurological signs following isolated parasagittal injury in asphyxia at term. Eur J Paediatr Neurol, 2008; 12: 359-365.
  • 2007
    1. Sato Y, Fukasawa T, Hayakawa M, Yatsuya H, Hatakeyama M, Ogawa A, Kuno K. A new method of blood sampling reduces pain for newborn infants: a prospective, randomized controlled clinical trial. Early. Hum. Dev., 2007; 83: 389-394.
    2. Nanba Y, Matsui K, Aida N, Sato Y, Toyoshima K, Kawataki M, Hoshino R, Ohyama M, Itani Y, Goto A, Oka A. Magnetic resonance imaging regional T1 abnormalities at term accurately predict motor outcome in preterm infants. Pediatrics., 2007; 120: e10-e19.
    3. Kakizawa H, Matsui F, Tokita Y, Hirano K, Ida M, Nakanishi K, Watanabe M, Sato Y, Okumura A, Kojima S, Oohira A. Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats. Early. Hum. Dev., 2007; 83: 535-540.
    4. Hayakawa M, Seo T, Itakua A, Hayashi S, Miyauchi M, Sato Y, Saito A, Nakayama A, Takemoto K, Hasegawa M, Kaneko K, Okada M, Hayakawa H, Sumigama S, Kikkawa F, Ando H, Kojima S. The MRI findings of the right-sided fetal lung can be used to predict postnatal mortality and the requirement for extracorporeal membrane oxygenation in isolated left-sided congenital diaphragmatic hernia. Pediatr. Res., 2007; 62: 93-97.
    5. Adachi M, Asakura Y, Sato Y, Tajima T, Nakajima T, Yamamoto T, Fujieda K. Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. Endocr. J., 2007; 54: 1003-1007.
  • 2006
    1. Hayakawa M, Takemoto K, Nakayama A, Saito A, Sato Y, Hasegawa M, Ieda K, Mimura S. An animal model of intrauterine growth retardation induced by synthetic thromboxane a(2). J. Soc. Gynecol. Investig., 2006; 13: 566-572.