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Sci Rep. 2019 Mar 11;9(1):4088. doi: 10.1038/s41598-019-40674-8.

Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.

Author information

1
Graduate School of Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
2
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan.
3
Department of Neonatology, National Hospital Organization Okayama Medical Center, Okayama, Japan.
4
Division of Neonatology, Shikoku Medical Center for Children and Adults, Kagawa, Japan.
5
Maternal and Perinatal Center, Kagawa University Hospital, Kagawa, Japan.
6
Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
7
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
8
Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan.
9
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. kusaka@med.kagawa-u.ac.jp.

Abstract

Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H2) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.5 ± 0.5 °C), and insult with hypothermia with H2 ventilation (TH-H2, 2.1-2.7%). H2 ventilation and TH were administered for 24 h. After ventilator weaning, neurological assessment was performed every 6 h for 5 days. On day 5, the brains of the piglets were harvested for histopathological analysis. Regarding the neurological score, the piglets in the TH-H2 group consistently had the highest score from day 2 to 5 and showed a significantly higher neurological score from day 3 compared with the NT group. Most piglets in the TH-H2 group could walk at day 3 of recovery, whereas walking ability was delayed in the two other groups. The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets.

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