Enhancement of Cognitive Function in Rats with Vascular Dementia Through Modulation of the Nrf2/GPx4 Signaling Pathway by High-Frequency Repetitive Transcranial Magnetic Stimulation

Physiol Res. 2024 Nov 19;73(5):857-868. doi: 10.33549/physiolres.935330.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive therapeutic modality acknowledged for augmenting neurological function recovery following stroke. Nonetheless, uncertainties remain regarding its efficacy in promoting cognitive function recovery in patients diagnosed with vascular dementia (VD). In this study, VD was experimentally induced in a rat model utilizing the bilateral common carotid artery occlusion method. Following a recuperation period of seven days, rats were subjected to high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) at a frequency of 10 Hz. Cognitive function was assessed utilizing the Morris water maze test, and the levels of IL-6, TNF-alpha, SOD, GSH, MDA, and Fe2+ in cerebral tissue were quantitatively analyzed through enzyme-linked immunosorbent assay. Moreover, the gene and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4) were meticulously investigated via quantitative polymerase chain reaction (qPCR) and Western blotting techniques. The use of HF-rTMS notably augmented cognitive function in rats with VD, concomitantly reducing neuroinflammation, oxidative stress, and ferroptosis within the brain. The group subjected to HF-rTMS demonstrated an increase in the levels of both proteins and genes associated with Nrf2 and GPx4, in comparison to the VD group. These results highlight the potential of HF-rTMS treatment in enhancing cognitive function in rats diagnosed with VD through the modulation of the Nrf2/GPx4 signaling pathway. This modulation, in turn, mitigates processes linked with neuroinflammation, oxidative stress, and ferroptosis. Nevertheless, additional studies are essential to comprehensively elucidate the underlying mechanisms and clinical implications of HF-rTMS treatment in the treatment of VD.

MeSH terms

  • Animals
  • Cognition* / physiology
  • Dementia, Vascular* / metabolism
  • Dementia, Vascular* / psychology
  • Dementia, Vascular* / therapy
  • Disease Models, Animal
  • Male
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress
  • Phospholipid Hydroperoxide Glutathione Peroxidase* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Signal Transduction*
  • Transcranial Magnetic Stimulation* / methods

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • glutathione peroxidase 4, rat