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Effect Of Axonal Damage And Remyelimation On Experimental Autoimmune Encephalomyelitis (EAE) After Administration Of Thyroid Hormone And Methylprednison In Rats.

Posted on:2009-10-27Degree:MasterType:Thesis
Country:ChinaCandidate:R LiFull Text:PDF
GTID:2144360245988414Subject:Pathology and pathophysiology
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Background and Objective Multiple sclerosis (MS) is an inflammatory -autoimmune disease with multiple foci of demyelination in the central nervous system (CNS). It is said that there were about 2,500,000 young patients all of the world.The cause and nosogenesis of MS is not known until now.It is general considered that it concerned with immune attack, viral infection, inheritation and so on. The diease of white matter damage as major event was caused by cellular immunity and humoral immunity together.There is no effective treatment to MS. Its treatment aim is to stop acute episode,prevent recrudescence and promote remyelination.The nerve stem cell has the self-renewal and the multi-differentiate potential.This multi-differentiate potential can turn NSCs into neurons and gliocytes(astrocytes and oligodendrocyte) under the special condition.Because oligodendrocyte is myelinating cell in CNS, it has the possibility through cellular substitution and axon remyelination to treat MS.Although the traditional medicine can reduce the symptom in MS, the remyelination is limited to axon, cannot enable the damaged axon to regenerate, thus curative effect is limited for the MS patient in mid and late stage. The research confirmed that thyroid hormone can induce NSCs to oligodendrocyte direction differentiation and mature. It provides a new way for MS treatment.Glucocorticosteroids(GCs) is one kind of immunity inhibitor and the anti-inflammatory agent widely applied in the clinical. It is used to treat the Experimental Autoimmune EncePhalomyelitis, especially acute stage and acute recrudescence stage. This research is for the purpose of discussing the effect on clinical symptom, inflammation cell infiltration, axon damage, demyelination as well as remyelination on EAE after administration of thyroid hormone and methylprednison in rats.Methods 40 Female Wistar big mice were Divided into 4 groups stochastically :EAE group ,MP group,T4group,MP+T4 group. MP group and MP+T4 group were given the corresponding dosage Methylprednisolone and T4 10d affter immunization. EAE group were given physiological saline. All animals were executed 30d after immunization. Hematoxylin-eosin staining,nerve special staining, immunohistochemistry and electronmicroscope were availed to observe curative effect by MP and T4 treatment.Results The clinical score respectively is 3.6, 2.38, 2.5, 1.5 in crest-time of the EAE group,the MP group,the T4 group and the Union group.Each treatment group compares with the EAE group has the significant difference (P<0.05), the union group compares with the MP group and the T4 group respectively also has the significant difference (P<0.05).The EAE group, the MP group, the T4 group and the union group achieve the crest-time respectively is (3.88±0.83)d,(2±0.71)d,(2.25±0.89)d and(1.38±0.52)d. Each treatment group compares with the EAE group has the significant difference (P<0.05), the union group compares with the MP group and the T4 group respectively also has the significant difference (P<0.05), the MP group compairs with the T4 group has not significant difference(P>0.05).Inflammation cell number in brain, cerebellum and spinal cord of each treatment group are decrease.The MP group and the union group compare with the EAE group respectively has the significant differenc(eP<0.05),the union group compares with the MP group has the significant difference(P<0.05),the T4 group compares with the EAE group has not the significant difference(P<0.05). Examination result of the areas of demyelination and axon damage demonstrated that each treatment group are all alleviate to a certain degree. Each treatment group compare with the EAE group respectively have the significant difference(P<0.05). The Union group compares with the MP group and the T4 group respectively also has the significant difference (P<0.05), The MBP immunohistochemistry result showed that each treatment group have more mature oligodendrocytes than the EAE group.The score of the EAE group,the MP group,the T4 group and the Union group respectively is 1.5,0.88,0.88,0.38. Each treatment group compare with the EAE group respectively have the significant difference(P<0.05). The Union group compares with the MP group and the T4 group respectively also has the significant difference (P<0.05).The T4 group and the Union group can be seen many myelins which is inappropriately thin for the corresponding axon by electron microscope, there are newborn myelin sheaths which are not achieve the normal proportion.Conclusions Methylprednisolone and T4 both can remit the clinical symptom of EAE,decrease demyelination and axonal damage in CNS. The curative effect of union medication is more remarkable.T4 can promote remyelination.
Keywords/Search Tags:Methylprednisolone, T4, Experimental Autoimmune Ence phalomyelitis, Axonal Damage, Remyelimation
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