Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?

Abstract

Currently, there is a lot of public interest in naturally occurring substances with medicinal properties that are minimally toxic, readily available and have an impact on health. Over the past decade, molecular hydrogen has gained the attention of both preclinical and clinical researchers. The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia. This review focuses on assessing the current state of knowledge about the neuroprotective effects of molecular hydrogen following ischemic brain injury. Recent studies in animal models of focal or global cerebral ischemia and cerebral ischemia in humans suggest that hydrogen has pleiotropic neuroprotective properties. One potential mechanism explaining some of the general health benefits of using hydrogen is that it may prevent aging-related changes in cellular proteins such as amyloid and tau protein. We also present evidence that, following ischemia, hydrogen improves cognitive and neurological deficits and prevents or delays the onset of neurodegenerative changes in the brain. The available evidence suggests that molecular hydrogen has neuroprotective properties and may be a new therapeutic agent in the treatment of neurodegenerative diseases such as neurodegeneration following cerebral ischemia with progressive dementia. We also present the experimental and clinical evidence for the efficacy and safety of hydrogen use after cerebral ischemia. The therapeutic benefits of gas therapy open up new promising directions in breaking the translational barrier in the treatment of ischemic stroke.

Study details

Article type

Systematic Review / Meta-Analysis

Disease / injury model

Post-ischemic neurodegeneration (including Alzheimer’s disease proteinopathy) following cerebral ischemia (stroke, cardiac arrest)

Dose comparison

The review discusses different concentrations (1-4% for inhalation, various doses for saline and water) and their effects on neuroprotection, indicating that higher concentrations and longer durations may increase efficacy.

Dose-dependent effect

Yes

Outcome

Mixed

Findings

Molecular hydrogen demonstrates significant neuroprotective effects in animal models and early clinical studies of post-ischemic neurodegeneration, including reduction of neuronal death, oxidative stress, neuroinflammation, amyloid and tau pathology, and improvement in cognitive and neurological outcomes. The evidence supports its potential as a therapeutic agent for neurodegenerative diseases following cerebral ischemia, with a favorable safety profile and pleiotropic mechanisms of action.