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Updated: Oct 7, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Stigmasterol attenuates cuprizone-induced neuroinflammation and demyelination in rats through modulation of
Rabeea Safdar1, Uzma Saleem2,3
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan. rabeeasafdar201@gmail.com.
Purpose:
Multiple sclerosis is a neuroinflammatory and demyelinating condition of brain with limited therapeutic options, many of which are associated with high treatment costs and adverse effects, In this research work, the neuroprotective potential of stigmasterol was investigated in a rat model of cuprizone-induced neuroinflammation and demyelination.
Materials And Methods:
A total of 36 Wistar rats (150-200 g) of both sexes were divided into 6 groups (n = 6) in random manner. Neuroinflammation and demyelination were induced by feeding animals a 0.3% cuprizone-containing diet for 5 weeks. Stigmasterol (100, 200, or 400 mg/kg/day) or dimethyl fumarate (15 mg/kg/day) was then administered orally for 3 weeks while cuprizone administration continued. After behavioral analysis, oxidative stress biomarkers, neurotransmitter levels, myelin-basic protein concentration by ELISA, mRNA expression of myelin basic protein and inflammatory cytokines, and histopathological alternations were evaluated.
Results:
Cuprizone administration pointedly increased oxidative stress, impaired behavioral performances, induced marked histopathological alterations, reduced mRNA expression of MBP and the anti-inflammatory cytokines, and elevated expression of inflammatory cytokines. Compared with cuprizone group, stigmasterol treatment prominently improved cognitive and locomotor performance (P < 0.001), restored antioxidant status (P < 0.001), upregulated the mRNA expression of IL-4, IL-10 and MBP, downregulated expression of IL-1β, TNF-α and IL-6, and increased both neurotransmitter concentrations (P < 0.001) and MBP concentrations in a dose-dependent manner. The effects of dimethyl fumarate were comparable to those observed with the highest dose of stigmasterol.
Conclusion:
Stigmasterol alleviated cuprizone-induced neuroinflammation, demyelination, oxidative stress and behavioral deficits while restoring MBP expression and modulating inflammatory cytokines expression. These results suggest that stigmasterol possesses neuroprotective and anti-inflammatory properties and warrants further investigation as an effective therapeutic candidate for demyelinating and neuroinflammatory disorders.
