Mesenchymal stem cells-derived exosomes and Kaempferol improve myelin repair via attenuating inflammation and oxidative stress in a cuprizone-induced demyelination model

BACKGROUND: Exosomes (EXOs), small vesicles secreted by cells, and kaempferol (KMP) as a natural flavonoid have anti-inflammatory and anti-oxidant activities. Here, we investigated the therapeutic potential of combination therapy of mesenchymal stem cell (MSC)-derived EXOs with KMP in a cuprizone (CPZ)-induced demyelination model. METHODS: Forty-five male C57BL/6J mice were used in this study. KMP was administered intracerebroventricularly and EXOs were delivered intranasally. Behavioral tests, tissue analyses, and molecular assays measured working memory, cognitive function, motor function, myelin integrity, oxidative stress, and inflammation. RESULTS: Behavioral assessments using Y-maze, novel arm discrimination, and wire hang tests revealed that the combination therapy significantly improved working memory, spatial recognition, and motor endurance compared to KMP or EXOs treated groups. Histological analyses demonstrated marked prevention of demyelination, as evidenced by enhanced myelin integrity on FluoroMyelin and Black-Gold II staining. At the molecular level, the combined treatment up regulated the antioxidant genes expression and regulated the activity of key antioxidant enzymes, while simultaneously reducing lipid peroxidation. Glial activation and pro-inflammatory cytokine genes expression were also reduced in the EXO + KMP treated mice. CONCLUSIONS: These findings suggest that combination therapy with EXOs and KMP improves myelin repair by targeting oxidative stress and neuroinflammation in a CPZ-induced demyelination model.