NIH Library of Medicine PubMed Central

Journal List > Med Gas Res > v.13(3): Jul-Sep 2023 > PNC9979207

Molecular Hydrogen Therapy For Neurological Diseases:
A Review Of Current Evidence

The review article titled "Molecular Hydrogen Therapy for Neurological Diseases: A Review of Current Evidence" discusses the potential therapeutic application of molecular hydrogen in treating various neurological diseases. The article highlights the role of oxidative stress and reactive oxygen species in the pathogenesis of neurological disorders. Molecular hydrogen therapy is presented as a promising approach due to its unique ability to selectively scavenge harmful free radicals while sparing essential reactive oxygen species.

The review covers animal and clinical studies that demonstrate the neuroprotective effects of hydrogen therapy in different neurological conditions, including stroke, neurodegenerative diseases, neurotrauma, and global brain injury.

The introduction outlines the significance of molecular hydrogen in scavenging reactive oxygen species and its potential therapeutic benefits. It emphasizes the relevance of oxidative stress in neurological diseases and the role of molecular hydrogen in addressing this issue.

The article details the delivery methods of hydrogen therapy, including inhalation of hydrogen gas, intravascular hydrogenized saline infusions, and orally consuming hydrogen water. It also discusses various studies that have investigated the distribution and effects of hydrogen based on different administration methods.

The review then delves into specific neurological conditions:

• Stroke: The review presents findings from animal models and clinical studies on ischemic stroke. It discusses hydrogen therapy's potential to reduce reperfusion injury, improve neurobehavioral outcomes, and alleviate oxidative stress.

• Intracerebral Hemorrhage: The potential neuroprotective effects of hydrogen therapy in animal models of hemorrhagic stroke are highlighted, although clinical studies in this context are lacking.

• Subarachnoid Hemorrhage (SAH): The article discusses the role of hydrogen therapy in reducing oxidative stress, inflammation, and neuronal apoptosis in SAH models. Some ongoing human studies are mentioned, evaluating the effects of hydrogen therapy in SAH patients.

• Neurodegenerative Diseases: The review discusses the beneficial effects of hydrogen therapy in animal models of Parkinson's and Alzheimer's diseases. It also includes a clinical trial demonstrating improved outcomes in Parkinson's patients receiving hydrogen water therapy.

• Neurotrauma: The potential neuroprotective effects of hydrogen therapy in traumatic brain injury (TBI) are discussed. Although larger clinical studies are lacking, anecdotal evidence suggests potential benefits in TBI cases.

• Global Brain Injury: The article presents studies on hydrogen therapy's effects in septic encephalopathy and global brain ischemia/reperfusion models.

The conclusion underscores the significant positive outcomes observed in preclinical and clinical studies of hydrogen therapy for neurological diseases. While more human studies are needed to further validate its efficacy, the review highlights hydrogen therapy's potential as an adjunctive treatment option for a wide range of neurological conditions. Notably, the article emphasizes the lack of reported adverse effects associated with hydrogen therapy in the reviewed studies.

分子氫療法治療神經系統疾病：對當前證據的回顧

題為“神經系統疾病的分子氫療法：當前證據的回顧”的評論文章討論了分子氫在治療各種神經系統疾病中的潛在治療應用。 該文章強調了氧化應激和活性氧在神經系統疾病發病機制中的作用。 分子氫療法因其獨特的選擇性清除有害自由基同時保留必需的活性氧的能力而被認為是一種有前途的方法。

該綜述涵蓋了動物和臨床研究，這些研究證明了氫療法對不同神經系統疾病（包括中風、神經退行性疾病、神經外傷和全腦損傷）的神經保護作用。

簡介概述了分子氫在清除活性氧方面的重要性及其潛在的治療益處。 它強調了氧化應激與神經系統疾病的相關性以及氫分子在解決這一問題中的作用。

文章詳細介紹了氫療法的輸送方法，包括吸入氫氣、血管內輸注氫化鹽水和口服氫水。 它還討論了基於不同管理方法調查氫的分佈和影響的各種研究。

然後，該評論深入研究了特定的神經系統疾病：

中風：該綜述介紹了缺血性中風動物模型和臨床研究的結果。 它討論了氫療法減少再灌注損傷、改善神經行為結果和減輕氧化應激的潛力。

腦出血：氫療法對出血性中風動物模型的潛在神經保護作用受到重視，儘管缺乏這方面的臨床研究。

蛛網膜下腔出血 (SAH)：本文討論了氫療法在減少 SAH 模型中氧化應激、炎症和神經元凋亡方面的作用。 提到了一些正在進行的人體研究，評估氫療法對 SAH 患者的效果。

神經退行性疾病：該綜述討論了氫療法對帕金森病和阿爾茨海默病動物模型的有益影響。 它還包括一項臨床試驗，證明接受氫水治療的帕金森病患者的治療效果有所改善。

神經創傷：討論了氫療法對創傷性腦損傷 (TBI) 的潛在神經保護作用。 儘管缺乏更大規模的臨床研究，但軼事證據表明 TBI 病例具有潛在的益處。

全球腦損傷：本文介紹了氫療法對膿毒性腦病和全球腦缺血/再灌注模型的影響的研究。

結論強調了氫療法治療神經系統疾病的臨床前和臨床研究中觀察到的顯著積極結果。 雖然需要更多的人體研究來進一步驗證其功效，但該評論強調了氫療法作為多種神經系統疾病的輔助治療選擇的潛力。 值得注意的是，該文章強調在審查的研究中缺乏與氫療法相關的不良反應的報導。

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Hydrogen, A Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, And Apoptosis

Molecular hydrogen (H2) is a colorless and odorless gas. Studies have shown that H2 inhalation has the therapeutic effects in many animal studies and clinical trials, and its application is recommended in the novel coronavirus pneumonia treatment guidelines in China recently. H2 has a relatively small molecular mass, which helps it quickly spread and penetrate cell membranes to exert a wide range of biological effects. It may play a role in the treatment and prevention of a variety of acute and chronic inflammatory diseases, such as acute pancreatitis, sepsis, respiratory disease, ischemia reperfusion injury diseases, autoimmunity diseases, etc.. H2 is primarily administered via inhalation, drinking H2-rich water, or injection of H2 saline. It may participate in the anti-inflammatory and antioxidant activity (mitochondrial energy metabolism), immune system regulation, and cell death (apoptosis, autophagy, and pyroptosis) through annihilating excess reactive oxygen species production and modulating nuclear transcription factor. However, the underlying mechanism of H2 has not yet been fully revealed. Owing to its safety and potential efficacy, H2 has a promising potential for clinical use against many diseases. This review will demonstrate the role of H2 in antioxidative, anti-inflammatory, and antiapoptotic effects and its underlying mechanism, particularly in coronavirus disease-2019 (COVID-19), providing strategies for the medical application of H2 for various diseases. 

分子氫（H2）是一種無色無味的氣體。 多項動物研究和臨床試驗研究表明，吸入H2具有治療作用，近期我國新冠肺炎治療指南推薦其應用。 H2的分子質量相對較小，這有助於它快速擴散和穿透細胞膜，發揮廣泛的生物效應。 可起到治療和預防多種急慢性炎症性疾病的作用，如急性胰腺炎、敗血症、呼吸系統疾病、缺血再灌注損傷疾病、自身免疫性疾病等。H2主要通過吸入、飲用H2給藥-富水，或註射H2鹽水。 它可能通過消除過量活性氧的產生和調節核轉錄因子來參與抗炎和抗氧化活性（線粒體能量代謝）、免疫系統調節和細胞死亡（細胞凋亡、自噬和細胞焦亡）。 然而，H2的潛在機制尚未完全揭示。 由於其安全性和潛在功效，H2 在臨床上用於治療多種疾病具有廣闊的前景。 本綜述將論證氫氣在抗氧化、抗炎和抗細胞凋亡方面的作用及其潛在機制，特別是在2019 年冠狀病毒病（COVID-19）中，為氫氣在各種疾病的醫學應用提供策略。

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Hydrogen, The Next Neuroprotective Agent?

This article discusses the potential neuroprotective effects of hydrogen in the context of acute ischemic stroke and reperfusion injury. It begins by highlighting the prevalence and impact of stroke in the United States, despite advancements in treatment.

The article emphasizes that cellular damage persists after blood flow is restored following an ischemic event. Current interventions have not identified a single viable molecule to address the complex pathological processes involved in stroke-induced damage.

Hydrogen has gained interest as a potential neuroprotectant due to its characteristics, including wide availability, rapid diffusion through cell membranes, inert nature, and ability to react with aggressive reactive oxygen species (ROS).

Reperfusion injury, known as the 'oxygen paradox,' involves excessive production of ROS following reperfusion of ischemic tissue. ROS, including hydroxyl, superoxide, and peroxynitrite, play roles in cell death and apoptosis pathways.

Hydrogen exhibits quenching capabilities that decrease lipid peroxidation, prevent DNA oxidation, and reduce glutamate toxicity-induced neuronal death. It also modulates cellular responses to oxidative stress, inflammation, and apoptosis pathways.

The article discusses the mechanisms by which hydrogen enhances mitophagy, increases antioxidant enzyme expression, and exerts anti-inflammatory effects. Studies have shown hydrogen's positive effects in animal models of ischemia, as well as in human studies where it was administered through inhalation or water.

The safety of hydrogen exposure has been demonstrated, and it holds promise as a neuroprotector during revascularization. The article concludes by advocating for larger randomized double-blind studies to further explore hydrogen's potential role in acute stroke treatment.

本文討論了氫氣在急性缺血性中風和再灌注損傷中的潛在神經保護作用。 首先強調了美國中風的患病率和影響，儘管治療方法取得了進步。

該文章強調，缺血事件後血流恢復後，細胞損傷仍然存在。 目前的干預措施尚未確定單一可行的分子來解決中風引起的損傷所涉及的複雜病理過程。

氫因其具有廣泛的可用性、通過細胞膜快速擴散、惰性以及與侵蝕性活性氧 (ROS) 反應的能力等特性，作為一種潛在的神經保護劑而受到關注。

再灌注損傷，被稱為“氧悖論”，涉及缺血組織再灌注後活性氧的過量產生。 ROS，包括羥基、超氧化物和過氧亞硝酸鹽，在細胞死亡和細胞凋亡途徑中發揮作用。

氫具有猝滅能力，可減少脂質過氧化、防止 DNA 氧化並減少谷氨酸毒性引起的神經元死亡。 它還調節細胞對氧化應激、炎症和細胞凋亡途徑的反應。

本文討論了氫增強線粒體自噬、增加抗氧化酶表達和發揮抗炎作用的機制。 研究表明，氫氣在缺血動物模型以及通過吸入或水給藥的人體研究中具有積極作用。

氫氣暴露的安全性已得到證實，並且有望在血運重建過程中作為神經保護劑。 文章最後提倡進行更大規模的隨機雙盲研究，以進一步探索氫氣在急性中風治療中的潛在作用。

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