The cuprizone model is a widely used tool for studying oligodendrocyte degeneration and remyelination in multiple sclerosis (MS). This model involves feeding young mice with cuprizone, which induces selective oligodendrocyte stress and subsequent demyelination. After 5–6 weeks of exposure, complete demyelination occurs, followed by endogenous remyelination if standard chow is provided. However, prolonged exposure leads to chronic demyelination and impaired remyelination. The model is valuable for investigating the mechanisms of demyelination and remyelination, as well as for testing potential therapeutic strategies to prevent oligodendrocyte degeneration or enhance remyelination. Oligodendrocyte degeneration in the cuprizone model is primarily due to mitochondrial dysfunction, ferroptosis, and endoplasmic reticulum stress. Apoptosis and ferroptosis are both involved in the degeneration process. The model allows for the study of cell death mechanisms, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The cuprizone model is particularly useful for studying the effects of drugs on oligodendrocyte survival and remyelination. Demyelination in the cuprizone model is most pronounced in the corpus callosum, with demyelination being more extensive in lateral areas and less so in the midline. The model is suitable for studying the effects of drugs on demyelination, with the best results obtained when demyelination is semimaximal and incomplete. The model also allows for the study of remyelination, with the most effective results obtained when remyelination is assessed during the early stages of recovery. Remyelination in the cuprizone model involves the activation and proliferation of oligodendrocyte progenitor cells (OPCs), which migrate to demyelinated axons and differentiate into mature oligodendrocytes. OPCs can originate from different sources, including progenitor cells in the brain and specific neurogenic niches. The model is useful for studying the role of various cell types in remyelination and for testing potential therapeutic strategies to enhance remyelination. The cuprizone model is a valuable tool for studying the pathogenesis of MS and for developing new therapeutic strategies. It allows for the study of various aspects of MS pathology, including oligodendrocyte degeneration, demyelination, and remyelination. The model is particularly useful for studying the effects of drugs on oligodendrocyte survival and remyelination. The model has been used to demonstrate the importance of vasculature-associated oligodendrocytes, the role of T-cells in de- and remyelination, and the effects of advanced imaging techniques on assessingThe cuprizone model is a widely used tool for studying oligodendrocyte degeneration and remyelination in multiple sclerosis (MS). This model involves feeding young mice with cuprizone, which induces selective oligodendrocyte stress and subsequent demyelination. After 5–6 weeks of exposure, complete demyelination occurs, followed by endogenous remyelination if standard chow is provided. However, prolonged exposure leads to chronic demyelination and impaired remyelination. The model is valuable for investigating the mechanisms of demyelination and remyelination, as well as for testing potential therapeutic strategies to prevent oligodendrocyte degeneration or enhance remyelination. Oligodendrocyte degeneration in the cuprizone model is primarily due to mitochondrial dysfunction, ferroptosis, and endoplasmic reticulum stress. Apoptosis and ferroptosis are both involved in the degeneration process. The model allows for the study of cell death mechanisms, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The cuprizone model is particularly useful for studying the effects of drugs on oligodendrocyte survival and remyelination. Demyelination in the cuprizone model is most pronounced in the corpus callosum, with demyelination being more extensive in lateral areas and less so in the midline. The model is suitable for studying the effects of drugs on demyelination, with the best results obtained when demyelination is semimaximal and incomplete. The model also allows for the study of remyelination, with the most effective results obtained when remyelination is assessed during the early stages of recovery. Remyelination in the cuprizone model involves the activation and proliferation of oligodendrocyte progenitor cells (OPCs), which migrate to demyelinated axons and differentiate into mature oligodendrocytes. OPCs can originate from different sources, including progenitor cells in the brain and specific neurogenic niches. The model is useful for studying the role of various cell types in remyelination and for testing potential therapeutic strategies to enhance remyelination. The cuprizone model is a valuable tool for studying the pathogenesis of MS and for developing new therapeutic strategies. It allows for the study of various aspects of MS pathology, including oligodendrocyte degeneration, demyelination, and remyelination. The model is particularly useful for studying the effects of drugs on oligodendrocyte survival and remyelination. The model has been used to demonstrate the importance of vasculature-associated oligodendrocytes, the role of T-cells in de- and remyelination, and the effects of advanced imaging techniques on assessing