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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.

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Graduate School of Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Neonatology, National Hospital Organization Okayama Medical Center, Okayama, Japan.
Division of Neonatology, Shikoku Medical Center for Children and Adults, Kagawa, Japan.
Maternal and Perinatal Center, Kagawa University Hospital, Kagawa, Japan.
Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan.


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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