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

Abstract

This study explores whether molecular hydrogen (H₂) 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 + H₂), 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 H₂ treatment. Histological examinations showed pyknotic neuronal morphologies and elevated reactive oxygen species (ROS) in the VaD hippocampus, whereas H₂ administration mitigated these alterations. Furthermore, VaD-induced downregulation of BCL2 was reversed in the VaD + H₂ 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 H₂ treatment, thereby restoring immunological balance. Transcriptomic evaluations confirmed that VaD suppressed key neuroprotective and anti-inflammatory genes, while H₂ treatment restored or enhanced their expression. Collectively, these findings highlight the neuroprotective and immuno-modulatory potential of molecular hydrogen, suggesting that H₂ supplementation may promote neuronal resilience, modulate T cell differentiation, and support cognitive recovery in vascular dementia.