The results of this study show that the neuronal TNFR have fundamentally different roles in CNS pathology in vivo, with signaling through neuronal TNFR1 and IKKβ promoting microglia responses and neurotoxicity in mouse demyelination models (Fig. 8A), and neuronal TNFR2 being involved in preconditioning protection in excitotoxicity, but not in inflammatory demyelination (Fig. 8B). This evidence concerns the gene TNFRSF1B and Peripheral demyelination.