Abstract: Objective To explore the mechanism about the expression of the hyperphosphorylated p38MAPK in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) mouse and its relationship to the axonal damage, and investigate the potential regulation of SB203580 to the damaged axons in the CNS of EAE mouse.Methods SJL/J mice were used to establish the EAE model. Brain and spinal cord of EAE mice in the model group, SB203580 group and control group were used respectively at different time points. Stained with HE and Luxol Fast Blue (LFB), also the immunohistochemical detection was conducted with parallel phosphorylation of p38MAPK antibody staining and APP staining at the same time. By image analysis system, the number of positive signals, the coverage and the average density value in the cytoplasm of neuron in white matter lesions were measured.Results The model of EAE mice induced by PLP peptide manifested significant neurological symptoms, signs and features of relapse and remitting. Demyelinating change was observed in local regional white matter region. Compared with the model group, SB203580 group changed lighter, with its behavioral observations and had a significant weight gain (P<0.01). In addition to the control group, amyloid precursor protein (APP) expression was detected in other groups at various time points. Compared to the model group, APP expression was slighter than in SB203580 group. The number of positive cells and strength was significantly lower in the SB203580 group (P<0.01); expression of p38MAPK in EAE mice was observed at the earlier 7th day after immunization. Compared to the model group, expression of SB203580 group was lighter, positive number and intensity decreased markedly (P<0.01).Conclusion p38MAPK blockers SB203580 can not only inhibit activation of the p38MAPK in EAE mice, but also effectively reduce expression of APP which is symbolic target of EAE axonal injury, it is confirmed that the p38MAPK is indeed involved in the EAE axonal injury.

Key words: experimental autoimmune encephalomyelitis, SJL/J mice, hyperphosphorylated p38MAPK, myloid precursor protein, axonal damage