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


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.


Hypoxia-ischemia Nitric oxide synthase PDGFα receptor MBP Development 

Abbreviations and Acronyms


Central nervous system


Cerebral palsy


cAMP response element-binding protein


Antibody that labels macrophage/microglia


Glial fibrillary acid protein


Hypoxia ischemia


Myelin basic protein


Nicotinamide adenine dinucleotide phosphate reduced diaphorase


Nicotinamide adenine dinucleotide phosphate reduced diaphorase positive






Nitric oxide


Nitric oxide synthase


Neuronal nitric oxide synthase


Inducible nitric oxide synthase


Platelet derived growth factor receptor alpha


Postnatal day 0, here considered as the day of birth

P2, 7, 9, 23

Postnatal day 2, 7, 9, and 23


Surgical control


Superior Medullary Vellum


Univariate analises of variance


World health organization



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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