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Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses

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Abstract

Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses’ brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.

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Acknowledgements

This work was supported by Carlos Chagas Filho Research Foundation of the State of Rio de Janeiro (Faperj; grant numbers E-26.102.190/2009, E-26/201.174/2014, E-26/203.024/2015), National Council for Scientific and Technological development (CNPq; grant number 470734/2012-4), and National Institutes for Science and Technology (INCT-NT grant number 465346/2014-6 and INCT-EN grant number 573577/2008-5).

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  1. Jean Pierre Mendes Lima and Danielle Rayêe contributed equally to this work.

Authors and Affiliations

  1. Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Jean Pierre Mendes Lima, Danielle Rayêe, Diego Szczupak, Anna Fonseca, Flavia Regina Souza Lima, Roberto Lent & Daniela Uziel

  2. National Institute of Translational Neuroscience, Ministry of Science and Technology, Rio de Janeiro, Brazil

    Danielle Rayêe, Diego Szczupak, Flavia Regina Souza Lima & Roberto Lent

  3. Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Thaia Silva-Rodrigues, Paula Ribeiro Paes Pereira, Ana Paula Miranda Mendonca, Marcus F. Oliveira & Antonio Galina

  4. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Clara Rodrigues-Ferreira

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  1. Jean Pierre Mendes Lima
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Lima, J.P.M., Rayêe, D., Silva-Rodrigues, T. et al. Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses. Mol Neurobiol 55, 8668–8679 (2018). https://doi.org/10.1007/s12035-018-1019-7

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