👤 Bijan Sadighi-Moghaddam

Multiple sclerosis is a demyelinating neurodegenerative disease, and its animal model, experimental autoimmune encephalomyelitis (EAE), exhibits immunological and clinical similarities. The study aimed to examine mechanisms underlying therapeutic effects of mesenchymal stem cell administration in EAE. C57BL/6 mice were separated into control and treatment groups (T1, T2, and T3); EAE was induced in all animals. Clinical examinations were conducted daily, and on 25th day, animals were sacrificed, and spinal cord was stained for histological analysis. Additionally, spleen cell proliferation assay, assessments of cytokine, and gene expression in both spinal cord and spleen cells were performed. The results indicated a significant reduction in clinical symptoms among treatment groups compared to control group. Histological analyses revealed decreased infiltration of lymphocytes into the spinal cord and reduced demyelinated areas in treatment groups compared to control group. Cytokine production of IL-10, TGF-β, and IL-4 were significantly enhanced and IFN-γ and TNF-α in treatment groups were decreased relative to control group. Also, gene expression of CTLA-4, PD-1, IL-27, and IL-33 indicated a significant increase in treatment groups. The administration of MSCs significantly improved clinical symptoms, attenuated inflammation, and reduced spinal cord demyelination in EAE, suggesting a potential protective effect on disease progression. Show less

Multiple sclerosis (MS) is the most typical chronic inflammatory, autoimmune demyelinating disease of the central nervous system (CNS) which leads to physical dysfunction and paralysis in patients. A commonly used animal model for this disease is experimental autoimmune encephalomyelitis (EAE). Daphnetin (7,8‑dihydroxycoumarin) has been reported to exert various pharmacological activities, such as being neuroprotective and anti‑inflammatory, together with having antioxidant, anticancer, and antiviral properties. Eight‑week‑old C57BL/6 female mice were segregated into 3 groups, namely 1) a control group receiving PBS, 2) a low‑dose treatment group receiving 2 mg/kg of daphnetin, and, 3) a high‑dose treatment group receiving 8 mg/kg of daphnetin. EAE was induced with a subcutaneous injection of a combination of myelin oligodendrocyte glycoprotein (MOG) and complete Freund's adjuvant. On the day of induction, and again two days later, mice were injected intraperitoneally with pertussis toxin. Histological studies showed low lymphocyte infiltration and demyelination in the high and low dose treated groups. The ratio of spleen Treg cells and the levels of IL‑4, IL‑10, TGF‑β, and IL‑33 enhanced significantly in the treatment group related to the control group. Furthermore, both IL‑27 and IL‑35 were also enhanced significantly in the treatment group compared to the control group. Moreover, the levels of IFN‑γ, TNF‑α, and IL‑17 displayed a noticeable reduction in the daphnetin treated group. Daphnetin appears to improve the disease by increasing the expression of anti‑inflammatory cytokines and transcription factors (IL‑4, IL‑10, IL‑33, GATA3, TGF‑β, FoxP3), and reducing the production of pro‑inflammatory cytokines and transcription factors (IFN‑γ, STAT4, T‑bet, IL‑17, STAT3, ROR‑γt, TNF‑α). Show less