Hydrogen Gas Protects Newborn Brains from Oxygen Loss Damage

Authors
Journal
Neuroscience
Year
DOI
10.1016/j.neuroscience.2021.12.024
Study Type
Mouse
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Hypoxic-Ischemic Encephalopathy
Body System
Nervous System

TL;DR

Hydrogen treatment can reduce brain damage and improve recovery after a lack of oxygen and blood flow in newborn mice, but this benefit depends on a specific protective protein called Nrf2.

Key Finding

Hydrogen gas reduced brain injury and inflammation in mice with oxygen deprivation, but only when the Nrf2 protective pathway was present and functional.

Summary

This mouse study investigated how hydrogen gas protects the brain from damage caused by lack of oxygen and blood flow (a condition called hypoxic-ischemic encephalopathy). Researchers found that hydrogen reduced brain injury, cell death, and inflammation by activating a protective pathway called Nrf2, which also reduced harmful molecules called free radicals and suppressed inflammatory signals. Importantly, when mice lacked the Nrf2 protein, hydrogen no longer provided protection, showing that this specific pathway is essential for hydrogen's protective effects.

Practical Takeaway

This is an early-stage mouse study that identifies a potential mechanism for how hydrogen might protect brain tissue from injury. However, it does not demonstrate that hydrogen would have the same effects in humans, and no human trials have been conducted. Much more research would be needed before any clinical applications could be considered.

Abstract

Hypoxia and ischemia cause neonatal encephalopathy and brain injury and can further result in cerebral palsy, cognitive impairment, growth restriction, and epilepsy. Induction of neuroprotection is a crucial therapeutic strategy for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). Hydrogen has neuroprotective effects against brain-related diseases. Inflammation and oxidative stress are the two main pathophysiological mechanisms in neonatal hypoxic-ischaemic injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an endogenous redox-sensitive transcription factor that participates in the antioxidant defence system through its effects on inflammation and oxidative stress. Herein, the research focuses on the mechanisms by which Nrf2 participates in the protection of hydrogen against HIE. The model of HIE was established by ligation of the right carotid artery and hypoxia in wild-type (WT) and Nrf2-/- mice. First, Nrf2 pathway activity was detected after hypoxia-ischaemia (HI) followed or not by hydrogen treatment. Brain injury, apoptosis, the inflammatory response, oxidative stress injury, and learning and memory function were assayed. We found that HI induced Nrf2 expression and signalling activation. Hydrogen alleviated the infarction volume, brain water content, neurological scores, apoptosis and long-term learning and memory functions after HI in WT mice but not in Nrf2-/- mice. Moreover, the oxidative products reactive oxygen species (ROS) and malondialdehyde (MDA) and the cytokines tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and High mobility group box 1 (HMGB1) were reduced and the antioxidant enzymes Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were upregulated by hydrogen treatment after HI in WT mice, but not in Nrf2-/- mice. In addition, the absence of Nrf2 abolished the suppressive effect of hydrogen on the expression of Nacht, Lrr, and Pyd domains-containing protein 3 (NLRP3) pathway members and p65 NF-κB after HI. Taken together, our findings showed that hydrogen alleviated cellular injury and apoptosis, neurobehavioural deficits, the inflammatory response and oxidative stress via the Nrf2-mediated NLRP3 and NF-κB pathways.