Hydrogen Gas Protects Newborn Brains from Birth Injury in Rat Study

Authors
Journal
Oxidative Medicine and Cellular Longevity
Year
DOI
10.1155/2020/6978784
Study Type
Rat
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Neonatal Hypoxic-Ischemic Encephalopathy
Body System
Nervous System

TL;DR

Breathing in hydrogen gas can help protect the brains of newborn rats from damage caused by a lack of oxygen and blood flow.

Key Finding

Hydrogen gas inhalation significantly reduced brain injury in newborn rats and improved neurological outcomes, with earlier treatment and longer duration providing greater protection.

Summary

Researchers tested whether breathing hydrogen gas could protect newborn rats' brains from damage caused by lack of oxygen and blood flow (a condition called hypoxic-ischemic brain injury). They found that hydrogen gas inhalation reduced brain damage, improved early neurological function, and enhanced learning and memory in adult rats. The protective effect worked better when treatment started soon after injury and lasted longer.

Practical Takeaway

This is an animal study in newborn rats, so results cannot be directly applied to humans yet. The findings suggest hydrogen gas may have protective effects against brain damage from oxygen deprivation through specific cellular pathways, but human clinical trials would be needed to determine if this approach is safe and effective for treating newborns with this condition.

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments. Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate. We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI). H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults. This protective effect was associated with initiation time and duration of sustained H2 inhalation. Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1). H2 activated extracellular signal-regulated kinase and c-Jun N-terminal protein kinase and dephosphorylated p38 mitogen-activated protein kinase (MAPK) in oxygen-glucose deprivation/reperfusion (OGD/R) nerve growth factor-differentiated PC12 cells. Inhibitors of MAPKs blocked H2-induced HO-1 expression. HO-1 small interfering RNA decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) and reversed the protectivity of H2 against OGD/R-induced cell death. These findings suggest that H2 augments cellular antioxidant defense capacity through activation of MAPK signaling pathways, leading to HO-1 expression and subsequent upregulation of PGC-1α and SIRT-1 expression. Thus, upregulation protects NGF-differentiated PC12 cells from OGD/R-induced oxidative cytotoxicity. In conclusion, H2 inhalation exerted protective effects on neonatal rats with HIBI. Early initiation and prolonged H2 inhalation had better protective effects on HIBI. These effects of H2 may be related to antioxidant, antiapoptotic, and anti-inflammatory responses. HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway. Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated.