Molecular Hydrogen Mediates Neurorestorative Effects After Stroke in Diabetic Rats: the TLR4/NF-κB Inflammatory Pathway.

Abstract

Diabetes mellitus amplifies inflammatory responses and constitutes an independent risk factor for stroke, worsening neurological outcomes. Using a middle cerebral artery occlusion (MCAO) model in diabetic rats, this study evaluated the effects of molecular hydrogen (H2) across multiple endpoints: blood glucose levels before and after MCAO, 48-hour cerebral edema and infarct volume, and 28-day body weight, survival rate, and neurological function. Levels of TLR4, NF-κB p65 phosphorylation, catecholamines, acetylcholine, and inflammatory mediators were also quantified. H2 administration improved survival, body weight, and long-term neurological function while significantly reducing inflammation through suppression of NF-κB phosphorylation. Blood glucose fluctuations associated with MCAO were also attenuated. Notably, the beneficial effects were independent of circadian rhythm, suggesting favorable translational properties. These findings indicate that H2 exerts neurorestoration in diabetic stroke conditions through modulation of the TLR4/NF-κB signaling axis.

Mechanism

H2 suppresses phosphorylation of NF-κB p65 within the TLR4/NF-κB signaling pathway, thereby reducing downstream inflammatory mediator production and promoting neurological recovery in diabetic stroke.