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

Abstract

Diabetes is an independent risk factor for stroke and amplifies inflammation. Diabetic stroke is associated with a higher risk of death and worse neural function. The identification of effective anti-inflammatory molecules with translational advantages is particularly important to promote perioperative neurorestorative effects. Applying molecular hydrogen, we measured blood glucose levels before and after middle cerebral artery occlusion (MCAO), 48-h cerebral oedema and infarct volumes, as well as 28-day weight, survival and neurological function. We also measured the levels of TLR4, NF-κB p65, phosphorylated NF-κB p65, catecholamines, acetylcholine and inflammatory factors. All measurements comprehensively showed the posi- tive effect and translational advantage of molecular hydrogen on diabetic stroke. Molecular hydrogen improved the weight, survival and long-term neurological function of rats with diabetic stroke and alleviated changes in blood glucose levels before and after middle cerebral artery occlusion (MCAO), but no difference in circadian rhythm was observed. Molecular hydrogen inhibited the phosphorylation of NF-κB and significantly reduced inflammation. Molecular hydrogen mediates neurorestorative effects after stroke in diabetic rats. The effect is independent of circadian rhythms, indicating translational advantages. The molecular mechanism is related to the TLR4/NF-κB pathway and inflammation.

Study details

Article type

Original Research

Disease / injury model

Diabetic stroke (middle cerebral artery occlusion in diabetic rats)

Duration

28 days

Dose comparison

Only one hydrogen concentration (42% H2) was used; no dose comparison performed.

Dose-dependent effect

No

Outcome

Positive

Findings

Molecular hydrogen treatment after stroke in diabetic rats improved survival, neurological function, reduced infarct volume, brain edema, and systemic inflammation, and inhibited TLR4/NF-κB pathway activation. The effect was independent of circadian rhythm, indicating translational potential.