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.
ABSTRACT
@# ObjectiveTo explore the mechanism causing the sex differences in experimental autoimmune encephalomyelitis (EAE).MethodsEAE model was established with PLP 139-151 in SJL/J mice. The sex differences of illness state were evaluated by neurologic score, and that of response of peripheral lymphocytes to autologous antigens were detected by methods of MTT and ELISA.ResultsThe onset time of female SJL mice was 15±2.1 days less than that of male ones (22±4.3 days), and the feature of diseases course of female mice was relapse after recovery, but that of male mice was transient. No significant differences were observed in T cell responses and interferon-γ productions between male and female mice (P>0.05). Male mice secreted more interleukin-4 than female mice (P<0.01).ConclusionThe sex differences of EAE in mice are due to peripheral lymphocytes secreting more interleukin-4 in male mice.
ABSTRACT
BACKGROUND: Experimental autoimmune encephalomyelitis has become the most classical animal model for multiple sclerosis. However, the experimental autoimmune encephalomyelitis model of China presented one-way course of disease. By using proteolipid protein 139-151 and proteolipid protein 178-191, relapse remitting experimental autoimmune encephalomyelitis models may be induced in SJL/J mice which were susceptible to immune, which have similar clinical situation, course and histologicallterations to multiple sclerosis.OBJECTIVE: To establish the relapse remitting experimental autoimmune encephalomyelitis mouse model induced by proteolipid protein, which has similar clinical situation, course and histological alterations to multiple sclerosis.DESIGN: Completely randomized controlled study.SETTING: The centre of Neuro-information, and Neurological Institute,General Hospital of Chinese PLA.MATERIALS: The study was carried out at the Laboratory of Neuro-pathology, General Hospital of Chinese PLA, from February to June 2004.Sixty female SJL/J mice with 8-12 weeks old were selected and randomly divided into proteolipid protein 139-151 group and proteolipid protein-178-191 group with 30 in each.INTERVENTIONS: After injected with proteolipid protein-139-151 or proteolipid protein-178-191, the models of relapse remitting experimental autoimmune encephalomyelitis were induced, and the body weight and neurological signs of each female SJL/J mouse were viewed. The tissue morphological changes of models were observed with hematoxylin and eosin and uxol fast blue stain.MAIN OUTCOME MEASURES: The neurological symptoms and signs,features of relapse and remitting and the perivascular inflammatory cell infiltration, demyelinated lesion of the model of experimental autoimmune encephalomyelitis mouse induced by two proteolipid protein peptides.RESULTS: All 60 mice entered the final analysis. ① Significant neurological symptoms, signs and features of relapse and remitting was manifested in the model of experimental autoimmune encephalomyelitis mouse induced by two proteolipid protein peptides. Obvious phenomena of perivascular inflammatory cuffing, satellitism, predominant perivascular inflammatory cell infiltration and demyelinated lesion were found in spinal and cerebral tissue. ②Changes of body mass: Before immunity, the body mass of mice in two groups was( 17. 84 ± 2.59) g and (17. 88 ± 0.52) g respectively. Onset of relapse of the mice in proteolipid protein-178-191 group was earlier and faster, their body mass had no distinctive change after immunization and the mean body mass was(23.52 ± 2.37) g till the 60th day. Meanwhile, Onset of relapse of the mice in proteolipid protein-139-151 group was later and slower. After the immunity, the body mass of mice was little decrease, and the body mass was (16. 70 ±0.46) g on the 60th day. ③ Neural functional scores: The highest functional scores in the two groups were not different(3.86 ± 1.10vs 3.71 ±1.05, t=0.49, P=0.628).CONCLUSION: The two different antigenic peptides of proteolipid protein can all cause the autoimmune response of central nervous system. Both models have the same characters of relapse and remitting and the severity has no significant difference. But compared with proteolipid protein 139- 151 group,onset and recover of the experimental autoimmune encephalomyelitis of the mice in proteolipid protein 178-191 group were earlier, as well as weight variance was larger, which maybe due to the different structure of two peptides.