Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model

This study explores whether molecular hydrogen (H<sub>2</sub>) administration can alleviate cognitive and immunological disturbances in a mouse model of vascular dementia (VaD). Adult male C57BL/6 mice underwent bilateral common carotid artery stenosis to induce VaD and were subsequently...

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Main Authors: Dain Lee, Hyunjun Jo, Jong-Il Choi
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/14/1/111
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author Dain Lee
Hyunjun Jo
Jong-Il Choi
author_facet Dain Lee
Hyunjun Jo
Jong-Il Choi
author_sort Dain Lee
collection DOAJ
description This study explores whether molecular hydrogen (H<sub>2</sub>) administration can alleviate cognitive and immunological disturbances in a mouse model of vascular dementia (VaD). Adult male C57BL/6 mice underwent bilateral common carotid artery stenosis to induce VaD and were subsequently assigned to three groups: VaD, VaD with hydrogen-rich water treatment (VaD + H<sub>2</sub>), and Sham controls. Behavioral assessments using open field and novel object recognition tests revealed that VaD mice exhibited anxiety-deficient behavior and memory impairment, both of which were reversed by H<sub>2</sub> treatment. Histological examinations showed pyknotic neuronal morphologies and elevated reactive oxygen species (ROS) in the VaD hippocampus, whereas H<sub>2</sub> administration mitigated these alterations. Furthermore, VaD-induced downregulation of BCL2 was reversed in the VaD + H<sub>2</sub> group, in parallel with increased IL-4 expression. Flow cytometric analyses revealed that VaD disrupted T regulatory cell homeostasis by significantly increasing their proportion, an effect reversed by H<sub>2</sub> treatment, thereby restoring immunological balance. Transcriptomic evaluations confirmed that VaD suppressed key neuroprotective and anti-inflammatory genes, while H<sub>2</sub> treatment restored or enhanced their expression. Collectively, these findings highlight the neuroprotective and immuno-modulatory potential of molecular hydrogen, suggesting that H<sub>2</sub> supplementation may promote neuronal resilience, modulate T cell differentiation, and support cognitive recovery in vascular dementia.
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spelling doaj-art-213255e710ee496e8821f9b8b1670e482025-01-24T13:19:31ZengMDPI AGAntioxidants2076-39212025-01-0114111110.3390/antiox14010111Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse ModelDain Lee0Hyunjun Jo1Jong-Il Choi2KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seoul 02841, Republic of KoreaDepartment of Neurosurgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Seoul 08308, Republic of KoreaDepartment of Neurosurgery, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Ansan 15355, Republic of KoreaThis study explores whether molecular hydrogen (H<sub>2</sub>) administration can alleviate cognitive and immunological disturbances in a mouse model of vascular dementia (VaD). Adult male C57BL/6 mice underwent bilateral common carotid artery stenosis to induce VaD and were subsequently assigned to three groups: VaD, VaD with hydrogen-rich water treatment (VaD + H<sub>2</sub>), and Sham controls. Behavioral assessments using open field and novel object recognition tests revealed that VaD mice exhibited anxiety-deficient behavior and memory impairment, both of which were reversed by H<sub>2</sub> treatment. Histological examinations showed pyknotic neuronal morphologies and elevated reactive oxygen species (ROS) in the VaD hippocampus, whereas H<sub>2</sub> administration mitigated these alterations. Furthermore, VaD-induced downregulation of BCL2 was reversed in the VaD + H<sub>2</sub> group, in parallel with increased IL-4 expression. Flow cytometric analyses revealed that VaD disrupted T regulatory cell homeostasis by significantly increasing their proportion, an effect reversed by H<sub>2</sub> treatment, thereby restoring immunological balance. Transcriptomic evaluations confirmed that VaD suppressed key neuroprotective and anti-inflammatory genes, while H<sub>2</sub> treatment restored or enhanced their expression. Collectively, these findings highlight the neuroprotective and immuno-modulatory potential of molecular hydrogen, suggesting that H<sub>2</sub> supplementation may promote neuronal resilience, modulate T cell differentiation, and support cognitive recovery in vascular dementia.https://www.mdpi.com/2076-3921/14/1/111vascular dementiamolecular hydrogenbilateral common carotid artery sclerosisischemiaantioxidantreactive oxygen species
spellingShingle Dain Lee
Hyunjun Jo
Jong-Il Choi
Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
Antioxidants
vascular dementia
molecular hydrogen
bilateral common carotid artery sclerosis
ischemia
antioxidant
reactive oxygen species
title Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
title_full Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
title_fullStr Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
title_full_unstemmed Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
title_short Molecular Hydrogen Modulates T Cell Differentiation and Enhances Neuro-Regeneration in a Vascular Dementia Mouse Model
title_sort molecular hydrogen modulates t cell differentiation and enhances neuro regeneration in a vascular dementia mouse model
topic vascular dementia
molecular hydrogen
bilateral common carotid artery sclerosis
ischemia
antioxidant
reactive oxygen species
url https://www.mdpi.com/2076-3921/14/1/111
work_keys_str_mv AT dainlee molecularhydrogenmodulatestcelldifferentiationandenhancesneuroregenerationinavasculardementiamousemodel
AT hyunjunjo molecularhydrogenmodulatestcelldifferentiationandenhancesneuroregenerationinavasculardementiamousemodel
AT jongilchoi molecularhydrogenmodulatestcelldifferentiationandenhancesneuroregenerationinavasculardementiamousemodel