Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosis.

摘要: Axon injury is a major determinant of the loss neurological function in patients with multiple sclerosis. It unclear, however, whether damage to axons an obligatory consequence demyelination or it independent process that occurs permissive environment demyelinated lesions. Previous investigations into role CD8 T cells and perforin Theiler murine encephalomyelitis virus model sclerosis have used mouse strains resistant infection. To test axon injury, we established perforin-deficient on H-2 histocompatibility complex background thereby removing confounding factors related viral biology this virus-susceptible strain. This permitted direct comparison clinical pathological parameters between perforin-competent mice. The extent was indistinguishable mice, but chronically infected mice exhibited preservation motor spinal despite presence cord demyelination. Thus, necessary insufficient for model; absence protects without impacting These results suggest key mediator lend additional support hypothesis are primarily responsible