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Study On The Pathogenesis And Therapy Of Experimental Allergic Encephalomyelitis

Posted on:2004-12-25Degree:MasterType:Thesis
Country:ChinaCandidate:Y J YuFull Text:PDF
GTID:2144360095957861Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Multiple sclerosis is a common inflammation and demyelination disease of the human's CNS (central nervous system),experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune demyelination disease of the animal's CNS and an animal model for the human multiple sclerosis(MS).MS usually strikes the youth (ages of 20 to 40),characterised by the limb's numbness and paralysis.Generally,it alterates between relapse and remission.However,every relapse is always accompanied by the disease's deteriorating further and increasing disability.Given that the impairment on the patients' physical,emotional,social function and life quality,MS is always considered as a difficult problem faced with the neuroscientists.In this paper,we used the EAE as the model of MS to discuss the EAE's pathogenesis in tissular, cellular and molecular level.Except that,this study was designed to observe the therapeutic effects of Prednisone,Minocycline and EGB761 respectively Roping that we could clarify the EAE's etiological and pathophysiological mechanisms. According to the experimental results,this study was also contributing to decide the strategy of the treatments.Forty England guinea pigs were involved in this study.Firstly,we emulsified the fresh Guinea pigs' spinal cord in saline with an equal volume of CFA, and then,Guniea pigs were immunized with 0.1ml emulsion to hind footpads of the animals for the initial induction of EAE.Experimetal animals were devided into five groups at randonrnormal group (n=8),model group (n=8), Prednisone-rreated group (n=8),Minocycline-treated group (n=8) and EGB761-treated group (n=8).Normal group animals were immuninized with saline and CFA;model group animals were immunized with emulsion (0.1ml) and saline;other three group animals,immediately after immunized with emulsion(0.1ml), were treated with Prednisone (0.14 mg/100g/d),Minocycline (1.10mg/100g/d) and EGB761 (1.67mg/100g/d) respectively.All animals were anesthetized with diethyl ether,collected the blood by medial canthuson on day 0,18 and 34 postimmunizationand the serum were frozen and stored at -80C.The normal animals before immunization and EAE animals which clinical score reached 2 point were performed to blood Rt assay and the normal animals and EAE animals in model group,which clinical score reached 2 point,performed to the MCV(motor conduction velocity,MCV),BAEP(brainstem auditory evoked potentials,BAEP), SEP(somatosensory evoked potentials,SEP). Everyday we observated animals' behavier and noted the clinical scores.After 5 weeks,Guinea pigs were deeply anesthetized and perfused with 100ml saline,followed by 200ml 1 % and 4% paraformaldehyde.Brain and spinal cords were removed,fixed in 4% paraformaldehyde and transected.Then light microscopes were performed in brain and spine cords histology.The concentration of EL-10 in serum samples were determined as an direct measurement by radioimmunization,IL-12 was by ELISA.The levels of the TGF- 3 ,MMP-2,NOS,CD3 were determined by immunohistochemistry.The results showed that:1.Generally conditions: Compared with the model's group, Prednisone and EGB761 markedly suppressed the clinical severity of both the initial phase of disease (day7-18) and the duration of subsequent remission-relapse (day23-35).However,Minocycline animals were similar with the model group.The clinical score even increased significantly in the remission-relapse phase(day26-35). 2.The results of blood Rt displayed that the numbers of MO and RBC,HGB and HCT decreased significantly in the EAE guinea pigs compared with the normal animals and MCH,MPV increased.( P<0.05).3.Compared with the normal group,there were significant increase in concentration of IL-10 and that of IL-12 increased clearly on day 18 and 34(P<0.05).Especially on day 18,it reached its peak.4.The assay of Evoked Potentials:the numbers of MCVR2 and MCVL2 in the EAE guinea pigs clearly decreased compared with the normal animals.The latent period of the SEPN1 elongated apparently and all the BAEPS were...
Keywords/Search Tags:Experimental Allergic Encephalomyelitis, Evoked Potential, IL-12, TGF-β
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