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

J Neuroimmune Pharmacol. 2023 Jun;18(1-2):90-99. doi: 10.1007/s11481-022-10051-w. Epub 2022 Jul 27.

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 positive 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. Molecular hydrogen (H2) affects outcomes of ischemic stroke with diabetes mellitus (DM).

Keywords: Circadian rhythm; Diabetes; Molecular hydrogen; Neuroinflammation; Stroke.

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Experimental* / complications
  • Hydrogen / pharmacology
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Inflammation
  • NF-kappa B / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Stroke* / complications
  • Stroke* / drug therapy
  • Toll-Like Receptor 4 / metabolism

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Blood Glucose
  • Hydrogen