Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system (CNS) and belongs to the most frequent causes of irreversible disability in younger people. During the disease course of MS and the corresponding animal model experimental autoimmune encephalomyelitis (EAE), both adaptive and innate immune cells infiltrate the CNS and initiate a progressing neuroinflammation. Especially during the progressive phase of chronic neuroinflammation, axonal degeneration is the main cause of disability. Previous experiments provided evidence for beneficial effects of T helper 2 lymphocytes (TH2) in experimental neurotrauma. T cell-mediated neuroprotection after CNS injury occurred independently of T cell receptor signaling and was mediated through TH2-derived interleukin- 4 (IL-4), which potentiated neurotrophin signaling to injured neurons. In this thesis, it is shown that different IL-4 receptor (IL-4R) types exist on murine cortical neurons in vitro, which can be activated by IL-4 treatment and support neuron survival after excitotoxic insult. Moreover, all data of the group indicate evidence for a fast and direct neuronal IL-4R signaling pathway in neurons via IRS1-PI3K-PKC signal transduction, independently of neurotrophin signaling. IL- 4R signaling pathway leads to cytoskeletal remodeling and axonal repair. Together, these findings demonstrate that IL-4 mediates neuroprotection and axonal regeneration of the injured CNS and leads the way to future clinical treatment strategies to repair axonal damage in chronic neuroinflammation, CNS injury or neurodegeneration.