Ferroptosis is an early event in EAE mice. A, B Representative plot and summary graph showing flow cytometric analysis of infiltrating CD4+ and CD8+ T cells in the CNS of EAE mice on different immunization days (n = 5). C The lipid peroxidation (MDA and LPO) and iron levels in the spinal cords of EAE mice (n = 5). D Mean clinical scores of EAE mice treated with Lip-1 beginning on Day 10 postimmunization (n = 6). ***P < 0.001. E, F Representative plot and quantified percentages of flow cytometric analysis of immune cells infiltrating the CNS of EAE mice treated with Lip-1 for 7 days beginning on Day 10 postimmunization (n = 4). G Mean clinical scores of EAE mice treated with Lip-1 on Days 17 and 23 postimmunization (n = 6). H Diagrammatic drawing of the generation of cortical AAV8-Acsl4-KD mice. I Immunofluorescent colabeling of ACSL4 (green) and neurons (pink). Scale bar, 100 μm, as indicated. J Mean clinical scores of EAE mice with cortical Acsl4 knockdown (n = 6). **P < 0.01; ***P < 0.001. K, L Representative plot and summary graph showing flow cytometric analysis of infiltrating CD4+ and CD8+ T cells in the CNS of cortical Acsl4-knockdown mice and controls (n = 4). The data are presented as the means ± SEM. One-way ANOVA with Tukey’s multiple comparisons test (B, C, F, L) and two-way ANOVA with Tukey’s multiple comparisons test (D, G) were used. P values are indicated