Hydrogen Sulfide Alleviates Demyelination, Behavioral and Motor Impairments in a Cuprizone-Induced Rat Model of Multiple Sclerosis
Bratislava Medical Journal, vol.126, no.7, pp.1237-1253, 2025 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 126 Issue: 7
- Publication Date: 2025
- Doi Number: 10.1007/s44411-025-00129-1
- Journal Name: Bratislava Medical Journal
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE
- Page Numbers: pp.1237-1253
- Keywords: Cuprizone, Hydrogen sulfide, Multiple sclerosis, Sodium hydrosulfide
- Kütahya Health Sciences University Affiliated: Yes
Abstract
Objectives: This study investigated the effects of the H2S donor sodium hydrosulfide (NaHS) on demyelination and behavioral deficits in a cuprizone (CPZ)-induced experimental rat model of MS. Methods: The rats were fed chow pellets supplemented with 1% CPZ for 5 weeks, and NaHS (50 and 100 μmol/kg) was administered during the last 2 weeks. For behavioral assessment, grip strength, passive avoidance, rota rod and elevated plus maze tests were performed. Nuclear factor kappa-B (NF-κB) and interleukin-1 beta (IL-1β) were measured to assess inflammation in brain tissue. Demyelination in the corpus callosum (CC) was assessed by immunohistochemistry for myelin basic protein (MBP), platelet-derived growth factor receptor α (PDGFRα) and Glial fibrillary acidic protein (GFAP). The TUNEL method was used to assess apoptosis. Results: Demyelination in the CC was reduced in the NaHS-treated groups. NaHS increased the amount of MBP and decreased the amount of PDGFRα and GFAP immunoreactive cells. NaHS reduced NF-κB, IL-1β levels, and the number of apoptotic cells in the brain tissue. In addition, NaHS improved muscle strength, motor coordination, learning and memory, and showed a significant anxiolytic effect. However, it was found that the beneficial effects of NaHS decreased at a high dose of 100 μmol/kg. Conclusion: H2S showed neuroprotective effects by reducing demyelination, inflammation and apoptosis in the CPZ-induced MS model. H2S also improved muscle strength, motor coordination, learning and memory and showed anxiolytic activity. Anti-inflammatory, anti-apoptotic and antioxidant effects may play a role in the neuroprotective effects of H2S.