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Prenatal Systemic Hypoxia-Ischemia and Oligodendroglia Loss in Cerebellum

  • Penha Cristina BarradasEmail author
  • Tiago Savignon
  • Alex C. Manhães
  • Frank Tenório
  • Alan P. da Costa
  • Marta C. Cunha-Rodrigues
  • Juliana Vaillant
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Hypoxia-ischemia Nitric oxide synthase PDGFα receptor MBP Development 

Abbreviations and Acronyms

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

Notes

Acknowledgments

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

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Penha Cristina Barradas
    • 1
    Email author
  • Tiago Savignon
    • 1
    • 3
  • Alex C. Manhães
    • 2
  • Frank Tenório
    • 1
  • Alan P. da Costa
    • 1
  • Marta C. Cunha-Rodrigues
    • 1
  • Juliana Vaillant
    • 1
  1. 1.Depto. Farmacologia e PsicobiologiaInstituto de Biologia—UERJRio de Janeiro, RJBrazil
  2. 2.Depto. Ciências Fisiológicas; Instituto de Biologia Roberto Alcantara GomesUniversidade do Estado do Rio de JaneiroRio de Janeiro, RJBrazil
  3. 3.Depto. Farmacologia e ToxicologiaInstituto Nacional de Controle de Qualidade em SaúdeRio de Janeiro, RJBrazil

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