Abstract
Background
Newborn pigs offer theoretical advantages for studying newborn hypoxic–ischemic (HI) brain damage because of a development and structure similar to the human brain. However, the correlation between functional features and actual HI brain damage has not been reported.
Methods
Newborn pigs were examined daily for 3 days after a HI insult using amplitude-integrated EEG (aEEG), and a neurobehavioral score enriched with stress and social and object interaction-driven activity evaluation. Brain damage was then assessed using histologic, immunohistochemical, and proton magnetic resonance spectroscopy studies. Brain concentration of several neurotransmitters was determined by HPLC.
Results
HI insult led to aEEG amplitude decrease, muscle tone and activity impairment, eating disorders, poor environmental interaction, and increased motionless periods. Basal aEEG amplitude, muscle tone, and general behavior were the best predictive items for histological and biochemical (lactate/N-acetylaspartate ratio) brain damage. Hyperexcitable response to stress correlated inversely with brain damage. Motionless time, which correlated with brain damage severity, was inversely related to brain concentration of dopamine and norepinephrine.
Conclusion
Standard neurologic examination of brain activity and motor and behavioral performance of newborn pigs is a valuable tool to assess HI brain damage, thus offering a powerful translational model for HI brain damage pathophysiology and management studies.
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Acknowledgements
We are indebted to Martin Santos, PhD, and María Dolores Molina Corzo for their help performing this experiment. We also thank Jason Willis-Lee MITI for medical writing assistance during preparation of the final manuscript. This work was supported by grants from the Carlos III Research Institute (ISCiii) according to the Spanish Plan for R + D + I 2008–2011 and the State Plan for Scientific and Technical Research and Innovation 2016–2019, with co-funding from the European Regional Development Funds (FEDER) (FIS- PI16/00689) and from the Biomedicine Program, Community of Madrid (S2010/BMD-2308).
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Substantial contributions to: Conception and design: J.M.-O., F.-J.A. Acquisition of data: L.B., A.C., H.L., J.M.-O. Analysis and interpretation of data: C.V., M.C., L.C., L.J.-S., M.R.P., J.M.-O. Drafting the article or revising it critically for important intellectual content: J.M.-O., F.-J.A. Final approval of the version to be published: all authors.
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Barata, L., Cabañas, A., Lafuente, H. et al. aEEG and neurologic exam findings correlate with hypoxic–ischemic brain damage severity in a piglet survival model. Pediatr Res 85, 539–545 (2019). https://doi.org/10.1038/s41390-019-0282-2
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DOI: https://doi.org/10.1038/s41390-019-0282-2
