Skip to main content
SpringerLink
Log in

Prenatal Systemic Hypoxia-Ischemia and Oligodendroglia Loss in Cerebellum

  • Chapter
  • First Online:
Glial Cells in Health and Disease of the CNS

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 949))

Abstract

Hypoxic-ischemic (HI) injury is an important cause of death and disabilities. Despite all improvements in neonatal care, the number of children who suffer some kind of injury during birth has remained stable in the last decade. A great number of studies have shown alterations in neural cells and many animal models have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI model in which the uterine arteries are temporarily clamped on the 18th gestation day. The findings were quite similar to the ones observed in postmortem studies. The white matter is clearly damaged, and a great amount of astrogliosis takes place both in the gray and white matters. Motor changes were also found but no data regarding the cerebellum, an important structure related to motor performance, was presented. Using this model, we have shown an increased level of iNOS at P0 and microgliosis and astrogliosis at P9, and astrogliosis at P23 (up to 4 weeks from the insult). NO is important in migration, maturation, and synaptic plasticity, but in exacerbated levels it may also contribute to cellular and tissue damage. We have also evaluated oligodendroglia development in the cerebellum. At P9 in HI animals, we found a decrease in the number of PDGFRα+ cells and an apparent delay in myelination, suggesting a failure in oligodendroglial progenitors migration/maturation and/or in the myelination process. These results point to an injury in cerebellar development that might help to explain the motor problems in HI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CNS:

Central nervous system

CP:

Cerebral palsy

CREB:

cAMP response element-binding protein

ED1:

Antibody that labels macrophage/microglia

GFAP:

Glial fibrillary acid protein

HI:

Hypoxia ischemia

MBP:

Myelin basic protein

NADPH-d:

Nicotinamide adenine dinucleotide phosphate reduced diaphorase

NADPH-d+:

Nicotinamide adenine dinucleotide phosphate reduced diaphorase positive

NM:

Non-manipulated

NMDA:

N-methyl-d-aspartate

NO:

Nitric oxide

NOS:

Nitric oxide synthase

nNOS:

Neuronal nitric oxide synthase

iNOS:

Inducible nitric oxide synthase

PDGFRα:

Platelet derived growth factor receptor alpha

P0:

Postnatal day 0, here considered as the day of birth

P2, 7, 9, 23:

Postnatal day 2, 7, 9, and 23

SHAM:

Surgical control

SMV:

Superior Medullary Vellum

uANOVA:

Univariate analises of variance

WHO:

World health organization

References

  • Adlinolfi M (1993) Infectious diseases in pregnancy, cytokines and neurological impairment: an hypothesis. Dev Med Child Neurol 35:549–553

    Article  CAS  PubMed  Google Scholar 

  • Back SA, Han BH, Luo NL et al (2002a) Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci 22:455–463

    CAS  PubMed  Google Scholar 

  • Back SA, Luo NL, Borenstein NS et al (2002b) Arrested oligodendrocyte lineage progression during human cerebral white matter development: dissociation between the timing of progenitor differentiation and myelinogenesis. J Neuropathol Exp Neurol 61:197–211

    Article  PubMed  Google Scholar 

  • Back SA, Craig A, Kayton RJ et al (2007) Hypoxia-ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter. J Cereb Blood Flow Metab 27:334–347. doi:10.1038/sj.jcbfm.9600344

    Article  CAS  PubMed  Google Scholar 

  • Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81:871–927

    CAS  PubMed  Google Scholar 

  • Chanez C, Rabin O, Heroux M, Giguere JF (1993) Cerebral amino acid changes in an animal model of intrauterine growth retardation. Metab Brain Dis 8:61–72

    Article  CAS  PubMed  Google Scholar 

  • Cummins SK, Nelson KB, Grether JK, Velie EM (1993) Cerebral palsy in four northern California counties, births 1983 through 1985. J Pediatr 123:230–237

    Google Scholar 

  • Dieni S, Rees S (2003) Dendritic morphology is altered in hippocampal neurons following prenatal compromise. J Neurobiol 55:41–52. doi:10.1002/neu.10194

    Article  PubMed  Google Scholar 

  • Folkerth RD, Haynes RL, Borenstein NS et al (2004) Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. J Neuropathol Exp Neurol 63:990–999

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb M, Matute C (1997) Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. J Cereb Blood Flow Metab 17:290–300. doi:10.1097/00004647-199703000-00006

    Article  CAS  PubMed  Google Scholar 

  • Grojean S, Schroeder H, Pourié G et al (2003) Histopathological alterations and functional brain deficits after transient hypoxia in the newborn rat pup: a long term follow-up. Neurobiol Dis 14:265–278. doi:10.1016/S0969-9961(03)00082-2

    Article  CAS  PubMed  Google Scholar 

  • Haynes V, Elfering SL, Squires RJ et al (2003) Mitochondrial nitric-oxide synthase: role in pathophysiology. IUBMB Life 55:599–603. doi:10.1080/15216540310001628681

    Article  CAS  PubMed  Google Scholar 

  • Jensen A, Klönne HJ, Detmer A, Carter AM (1996) Catecholamine and serotonin concentrations in fetal guinea-pig brain: relation to regional cerebral blood flow and oxygen delivery in the growth-restricted fetus. Reprod Fertil Dev 8:355–364

    Article  CAS  PubMed  Google Scholar 

  • Kashiwagi K, Iizuka Y, Mochizuki S et al (2003) Differences in nitric oxide production: a comparison of retinal ganglion cells and retinal glial cells cultured under hypoxic conditions. Brain Res Mol Brain Res 112:126–134

    Article  CAS  PubMed  Google Scholar 

  • Kaur C, Sivakumar V, Foulds WS (2006) Early response of neurons and glial cells to hypoxia in the retina. Invest Ophthalmol Vis Sci 47:1126–1141. doi:10.1167/iovs.05-0518

    Article  PubMed  Google Scholar 

  • Kuban KC, Leviton A (1994) Cerebral palsy. N Engl J Med 330:188–195. doi:10.1056/NEJM199401203300308

    Article  CAS  PubMed  Google Scholar 

  • Lawn J, Shibuya K, Stein C (2005) No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bull World Health Organ 83:409–417

    PubMed  PubMed Central  Google Scholar 

  • Le Mellédo J-MM, Mahil N, Baker GB (2004) Nitric oxide: a key player in the relation between cardiovascular disease and major depressive disorder? J Psychiatry Neurosci 29:414–416

    Google Scholar 

  • Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17

    CAS  PubMed  PubMed Central  Google Scholar 

  • Loeliger M, Watson CS, Reynolds JD et al (2003) Extracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep. Neuroscience 116:705–714

    Article  CAS  PubMed  Google Scholar 

  • Marín-Padilla M (1997) Developmental neuropathology and impact of perinatal brain damage. II: white matter lesions of the neocortex. J Neuropathol Exp Neurol 56:219–235

    Article  PubMed  Google Scholar 

  • Marín-Padilla M (1999) Developmental neuropathology and impact of perinatal brain damage. III: gray matter lesions of the neocortex. J Neuropathol Exp Neurol 58:407–429

    Article  PubMed  Google Scholar 

  • Mazur M, Miller RH, Robinson S (2010) Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury. J Neurosurg Pediatr 6:206–221. doi:10.3171/2010.5.PEDS1032

    Article  PubMed  PubMed Central  Google Scholar 

  • Minkowski A, Chanez C, Priam M et al (1981) Long lasting effects of intrauterine malnutrition on neurotransmitters metabolism in the brain of developing rats. Prog Clin Biol Res 77:643–660

    CAS  PubMed  Google Scholar 

  • Mishra O, Mishra R, Ashraf Q, Delivoria-Papadopoulos M (2006) Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets. Neuroscience 140:857863. doi:10.1016/j.neuroscience.2006.02.060

    Article  Google Scholar 

  • Morand O, Chanez C, Masson M et al (1982) Alteration in fatty acid composition of neurons, astrocytes, oligodendrocytes, myelin and synaptosomes in intrauterine malnutrition in rat. Ann Nutr Metab 26:111–120

    Article  CAS  PubMed  Google Scholar 

  • Nelson KB, Grether JK, Dambrosia JM et al (2003) Neonatal cytokines and cerebral palsy in very preterm infants. Pediatr Res 53:600–607. doi:10.1203/01.PDR.0000056802.22454.AB

    Article  CAS  PubMed  Google Scholar 

  • Olivier P, Baud O, Evrard P et al (2005) Prenatal ischemia and white matter damage in rats. J Neuropathol Exp Neurol 64:998–1006

    Article  PubMed  Google Scholar 

  • Park SY, Lee H, Hur J et al (2002) Hypoxia induces nitric oxide production in mouse microglia via p38 mitogen-activated protein kinase pathway. Brain Res Mol Brain Res 107:9–16

    Article  CAS  PubMed  Google Scholar 

  • Perlman JM, Risser R, Broyles RS (1996) Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors. Pediatrics 97:822–827

    CAS  PubMed  Google Scholar 

  • Pfeiffer SE, Warrington AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191–197

    Article  CAS  PubMed  Google Scholar 

  • Reynolds R, Wilkin GP (1988) Development of macroglial cells in rat cerebellum. II. An in situ immunohistochemical study of oligodendroglial lineage from precursor to mature myelinating cell. Development 102:409–425

    CAS  PubMed  Google Scholar 

  • Rice JE, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9:131–141. doi:10.1002/ana.410090206

    Article  PubMed  Google Scholar 

  • Robinson S, Petelenz K, Li Q et al (2005) Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis 18:568–581. doi:10.1016/j.nbd.2004.10.024

    Article  CAS  PubMed  Google Scholar 

  • Sadiq HF, Das UG, Tracy TF, Devaskar SU (1999) Intra-uterine growth restriction differentially regulates perinatal brain and skeletal muscle glucose transporters. Brain Res 823:96–103

    Article  CAS  PubMed  Google Scholar 

  • Savignon T, Costa E, Tenorio F et al (2012) Prenatal hypoxic-ischemic insult changes the distribution and number of NADPH-diaphorase cells in the cerebellum. PLoS ONE 7:e35786. doi:10.1371/journal.pone.0035786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spinillo A, Capuzzo E, Stronati M et al (1998) Obstetric risk factors for periventricular leukomalacia among preterm infants. Br J Obstet Gynaecol 105:865–871

    Article  CAS  PubMed  Google Scholar 

  • Tashima L, Nakata M, Anno K et al (2001) Prenatal influence of ischemia-hypoxia-induced intrauterine growth retardation on brain development and behavioral activity in rats. Biol Neonate 80:81–87

    Article  CAS  PubMed  Google Scholar 

  • Terzidou V, Bennett P (2001) Maternal risk factors for fetal and neonatal brain damage. Biol Neonate 79:157–162

    Article  CAS  PubMed  Google Scholar 

  • Thorburne SK, Juurlink BH (1996) Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J Neurochem 67:1014–1022

    Article  CAS  PubMed  Google Scholar 

  • Vannucci RC, Vannucci SJ (2005) Perinatal hypoxic-ischemic brain damage: evolution of an animal model. Dev Neurosci 27:81–86. doi:10.1159/000085978

    Article  CAS  PubMed  Google Scholar 

  • Verma U, Tejani N, Klein S et al (1997) Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate. Am J Obstet Gynecol 176:275–281

    Article  CAS  PubMed  Google Scholar 

  • Vexler ZS, Yenari MA (2009) Does inflammation after stroke affect the developing brain differently than adult brain? Dev Neurosci 31:378–393. doi:10.1159/000232556

    Google Scholar 

  • Volpe JJ (2001) Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 50:553–562. doi:10.1203/00006450-200111000-00003

    Article  CAS  PubMed  Google Scholar 

  • Volpe JJ (2003) Cerebral white matter injury of the premature infant-more common than you think. Pediatrics 112:176–180

    Article  PubMed  Google Scholar 

  • Volpe J (2009) Cerebellum of the premature infant: rapidly developing, vulnerable, clinically important. J Child Neurol 24:10851104. doi:10.1177/0883073809338067

    Article  Google Scholar 

  • Wigglesworth (1964) Experimental growth retardation in the foetal rat. J Pathol Bacteriol 88:1–13

    Google Scholar 

  • Wu YW, Colford JM (2000) Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis. JAMA 284:1417–1424

    Article  CAS  PubMed  Google Scholar 

  • You Y, Kaur C (2000) Expression of induced nitric oxide synthase in amoeboid microglia in postnatal rats following an exposure to hypoxia. Neurosci Lett 279:101–104

    Article  CAS  PubMed  Google Scholar 

  • Zubrow AB, Delivoria-Papadopoulos M, Ashraf QM et al (2002a) Nitric oxide-mediated expression of Bax protein and DNA fragmentation during hypoxia in neuronal nuclei from newborn piglets. Brain Res 954:60–67

    Article  CAS  PubMed  Google Scholar 

  • Zubrow AB, Delivoria-Papadopoulos M, Ashraf QM et al (2002b) Nitric oxide-mediated Ca2+/calmodulin-dependent protein kinase IV activity during hypoxia in neuronal nuclei from newborn piglets. Neurosci Lett 335:5–8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Jorge Pereira das Neves for technical assistance and Mariana Soares Magalhães for animal care.

Author information

Authors and Affiliations

  1. Depto. Farmacologia e Psicobiologia, Instituto de Biologia—UERJ, Av. 28 de setembro, 87 fds 5° andar, Rio de Janeiro, RJ, 20551-030, Brazil

    Penha Cristina Barradas, Tiago Savignon, Frank Tenório, Alan P. da Costa, Marta C. Cunha-Rodrigues & Juliana Vaillant

  2. Depto. Ciências Fisiológicas; Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20551-030, Brazil

    Alex C. Manhães

  3. Depto. Farmacologia e Toxicologia, Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-900, Brazil

    Tiago Savignon

Authors
  1. Penha Cristina Barradas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiago Savignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alex C. Manhães
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frank Tenório
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alan P. da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta C. Cunha-Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juliana Vaillant
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Penha Cristina Barradas .

Editor information

Editors and Affiliations

  1. Faculty of Medicine Professor of Neurology, Pontificia Universidad Católica de Chile, Santiago, Chile

    Rommy von Bernhardi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Barradas, P.C. et al. (2016). Prenatal Systemic Hypoxia-Ischemia and Oligodendroglia Loss in Cerebellum. In: von Bernhardi, R. (eds) Glial Cells in Health and Disease of the CNS. Advances in Experimental Medicine and Biology, vol 949. Springer, Cham. https://doi.org/10.1007/978-3-319-40764-7_16

Download citation

Publish with us

Policies and ethics

Search

Navigation