Fig. 1.

A Representation of commonly used cuprizone exposure protocol. Rodents are fed with concentrations of typically 0.2 – 0.3% (w/w) cuprizone in animal chow for up to 6 weeks to study acute demyelination and 12 weeks to study chronic demyelination. This is sometimes followed by a period of normal chow without cuprizone (withdrawl) to induce remyelination. B Time course of cuprizone intoxication in the corpus callosum. The dashed black line represents myelin integrity, and the colored lines represent cellularity (numbers of cells, unless stated otherwise) of microglia/macrophages in red, astrocytes in blue (here cellularity refers to reactivity), T-cells in teal, and neutrophils in purple. Below the timeline we show different modes of cell death observed in the cuprizone model, and their time of occurrence depicted by the black bar. Apoptosis (green box) occurs between day 2 and 3 weeks. Ferroptosis markers are elevated (yellow box) between day 2 and 4 weeks. Necroptosis (brown box) is seen in the cuprizone model between week 2 and week 5. Inflammasome-mediated cell death/pyroptosis (grey box) occurs between 3 and 5 weeks