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Disease Markers
Volume 2018 (2018), Article ID 5046372, 9 pages
https://doi.org/10.1155/2018/5046372
Research Article

Cerebellum Susceptibility to Neonatal Asphyxia: Possible Protective Effects of N-Acetylcysteine Amide

1Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
2Department for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway
3University of Oslo, Oslo, Norway
4Aix Marseille Université, CNRS, NICN, Marseille, France
5Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
6Department of Neonatology, Karolinska University Hospital, Stockholm, Sweden
7Department of Pathology, Oslo University Hospital, Ullevål, University of Oslo, Oslo, Norway
8Department of Women’s and Children’s Health, Division of Paediatric Endocrinology, Karolinska Institutet, Stockholm, Sweden
9Department of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway

Correspondence should be addressed to T. Benterud

Received 1 May 2017; Revised 7 September 2017; Accepted 7 December 2017; Published 30 January 2018

Academic Editor: Hubertus Himmerich

Copyright © 2018 T. Benterud et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. After perinatal asphyxia, the cerebellum presents more damage than previously suggested. Objectives. To explore if the antioxidant N-acetylcysteine amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a neonatal pig model. Methods. Twenty-four newborn pigs in two intervention groups were exposed to 8% oxygen and hypercapnia, until base excess fell to −20 mmol/l or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they received either NACA (NACA group, ) or saline (vehicle-treated group, ). One sham-operated group () served as a control and was not subjected to hypoxia. Observation time after the end of hypoxia was 9.5 hours. Results. The intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle-treated pigs was significantly higher than that in sham controls (). Treatment with NACA was associated with a trend to decreased intranuclear proteolytic activity (), There were significantly less mutations in the mtDNA of the NACA group compared with the vehicle-treated group, 2.0 × 10−4 (±2.0 × 10−4) versus 4.8 × 10−5(±3.6 × 10−4, ). Conclusion. We found a trend to lower proteolytic activity in the core of Purkinje cells and significantly reduced mutation rate of mtDNA in the NACA group, which may indicate a positive effect of NACA after neonatal hypoxia. Measuring the proteolytic activity in the nucleus of Purkinje cells could be used to assess the effect of different neuroprotective substances after perinatal asphyxia.