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Antioxidants
Volume 14
Issue 12
10.3390/antiox14121405
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic–Ischemic Encephalopathy

by
Emma Balog
1,2,*,†,
Gábor Remzső
1,†,
Valéria Tóth-Szűki
1,
Éva Rózsa
1,2,
Viktória Kovács
1 and
Ferenc Domoki
1,*
1
Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary
2
Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged (IKIKK), 6720 Szeged, Hungary
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2025, 14(12), 1405; https://doi.org/10.3390/antiox14121405
Submission received: 23 September 2025 / Revised: 12 November 2025 / Accepted: 17 November 2025 / Published: 25 November 2025
(This article belongs to the Special Issue Hydrogen and Oxidative Stress: Implications for Health and Longevity)
Versions Notes

Abstract

Neonatal hypoxic–ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and long-term disability, despite therapeutic hypothermia (TH) treatment, underscoring the need for further preclinical research. In the present study, we compared the neuroprotection afforded by TH and inhaled molecular hydrogen (H2) treatment in a translational newborn pig HIE model. Following 20 min of asphyxia induced by a hypoxic/hypercapnic gas mixture, piglets were reoxygenated and monitored for 48 h. Animals were randomly assigned to normothermia, continuous H2 ventilation (2.1%), or TH (33.5 °C for 37 h followed by slow rewarming) groups. Physiological parameters, electroencephalography (EEG), visual evoked potentials (VEPs), and neuropathology were assessed. TH eliminated post-asphyxia seizures and improved VEP latency, while H2 delayed seizure onset and increased quantitative EEG markers of signal complexity. Neuropathology revealed severe thalamic injury in normothermic controls, which was significantly attenuated by both H2 and TH, while neocortical, hippocampal, and basal ganglia injury was less extensive and not significantly altered by either of the neuroprotective interventions. These findings demonstrate that continuous H2 inhalation provides neuroprotection in HIE comparable to TH, particularly in the thalamus. H2 also exerts distinct electrophysiological effects, suggesting its therapeutic potential as a treatment for neonatal HIE.
Keywords: hypoxic-ischemic encephalopathy; perinatal asphyxia; therapeutic hypothermia; molecular hydrogen; piglet model hypoxic-ischemic encephalopathy; perinatal asphyxia; therapeutic hypothermia; molecular hydrogen; piglet model

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MDPI and ACS Style

Balog, E.; Remzső, G.; Tóth-Szűki, V.; Rózsa, É.; Kovács, V.; Domoki, F. Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic–Ischemic Encephalopathy. Antioxidants 2025, 14, 1405. https://doi.org/10.3390/antiox14121405

AMA Style

Balog E, Remzső G, Tóth-Szűki V, Rózsa É, Kovács V, Domoki F. Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic–Ischemic Encephalopathy. Antioxidants. 2025; 14(12):1405. https://doi.org/10.3390/antiox14121405

Chicago/Turabian Style

Balog, Emma, Gábor Remzső, Valéria Tóth-Szűki, Éva Rózsa, Viktória Kovács, and Ferenc Domoki. 2025. "Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic–Ischemic Encephalopathy" Antioxidants 14, no. 12: 1405. https://doi.org/10.3390/antiox14121405

APA Style

Balog, E., Remzső, G., Tóth-Szűki, V., Rózsa, É., Kovács, V., & Domoki, F. (2025). Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic–Ischemic Encephalopathy. Antioxidants, 14(12), 1405. https://doi.org/10.3390/antiox14121405

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