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
• faktor 2 související s NF-E2 * metabolismus   MeSH
• fosfolipidová hydroperoxidglutathionperoxidasa * metabolismus   MeSH
• kognice * fyziologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• signální transdukce * MeSH
• transkraniální magnetická stimulace * metody   MeSH
• vaskulární demence * metabolismus   terapie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 * MeSH
• fosfolipidová hydroperoxidglutathionperoxidasa * MeSH
• glutathione peroxidase 4, rat MeSH Prohlížeč
• Nfe2l2 protein, rat MeSH Prohlížeč

The present study aimed to elucidate the effect of sulforaphane (a natural isothiocyanate) on oxidative stress and mitochondrial dysfunction during and at selected periods following status epilepticus (SE) induced in immature 12-day-old rats by Li-pilocarpine. Dihydroethidium was employed for the detection of superoxide anions, immunoblot analyses for 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels and respiratory chain complex I activity for evaluation of mitochondrial function. Sulforaphane was given i.p. in two doses (5 mg/kg each), at PD 10 and PD 11, respectively. The findings of the present study indicate that both the acute phase of SE and the early period of epileptogenesis (1 week and 3 weeks following SE induction) are associated with oxidative stress (documented by the enhanced superoxide anion production and the increased levels of 3-NT and 4-HNE) and the persisting deficiency of complex I activity. Pretreatment with sulforaphane either completely prevented or significantly reduced markers of both oxidative stress and mitochondrial dysfunction. Since sulforaphane had no direct anti-seizure effect, the findings suggest that the ability of sulforaphane to activate Nrf2 is most likely responsible for the observed protective effect. Nrf2-ARE signaling pathway can be considered a promising target for novel therapies of epilepsy, particularly when new compounds, possessing inhibitory activity against protein-protein interaction between Nrf2 and its repressor protein Keap1, with less "off-target" effects and, importantly, with an optimal permeability and bioavailability properties, become available commercially.

• Klíčová slova
• Immature rats, Mitochondrial dysfunction, Oxidative stress, Protection, Status epilepticus, Sulforaphane,
• MeSH
• faktor 2 související s NF-E2 * metabolismus   MeSH
• isothiokyanatany farmakologie   MeSH
• KEAP-1 metabolismus   MeSH
• krysa rodu Rattus MeSH
• mitochondrie metabolismus   MeSH
• oxidační stres MeSH
• status epilepticus * metabolismus   MeSH
• sulfoxidy metabolismus   farmakologie   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 * MeSH
• isothiokyanatany MeSH
• KEAP-1 MeSH
• sulforaphane MeSH Prohlížeč
• sulfoxidy MeSH
• superoxidy MeSH

Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological changes. Oxidative stress helps to regulate cellular phenotypes in physiological and pathological conditions. Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) transcription factor functions as a target nuclear receptor against oxidative stress and is a key factor in redox regulation in hypertension and cardiovascular disease. Nrf2 mediates transcriptional regulation of a variety of target genes. The Keap1-Nrf2-ARE system regulates many detoxification and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress. Keap1 normally maintains Nrf2 in the cytosol and stimulates its degradation through ubiquitination. During acute oxidative stress, oxidized molecules modify the interaction of Nrf2 and Keap1, when Nrf2 is released from the cytoplasm into the nucleus where it binds to the antioxidant response element (ARE). This triggers the expression of antioxidant and detoxification genes. The consequence of long-term chronic oxidative stress is activation of glycogen synthase kinase 3beta (GSK-3beta) inhibiting Nrf2 activity and function. PPARgamma (peroxisome proliferator-activated receptor gamma) is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension and metabolic syndrome. PPARgamma targeting of genes with peroxisome proliferator response element (PPRE) has led to the identification of several genes involved in lipid metabolism or oxidative stress. PPARgamma stimulation is triggered by endogenous and exogenous ligands - agonists and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway. Nrf2 and PPARgamma are linked together with their several activators and Nrf2/ARE and PPARgamma/PPRE pathways can control several types of diseases.

• MeSH
• antioxidační responzivní elementy MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• hypertenze metabolismus   patofyziologie   MeSH
• kardiovaskulární nemoci metabolismus   patofyziologie   MeSH
• KEAP-1 metabolismus   MeSH
• krevní tlak * MeSH
• lidé MeSH
• oxidační stres * MeSH
• PPAR gama metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• KEAP-1 MeSH
• PPAR gama MeSH
• reaktivní formy kyslíku MeSH