The Study Of Axon Damage In Experimental Autoimmune Encephalomyelitis And Imageology Characteristics Of Tumor-like Inflammatory Demyelinating Diseases

Background and Purpose:Multiple sclerosis ( MS) was a relatively common inflammatory demyelinating diseases of central nervous system(CNS).Experimental autoimmune encephalomyelitis (EAE) was the main animal model of MS. In recent years, with the progres of pathology, the axonal injury was found in the early stage of onset in MS and EAE, EAE pathogenesis of axonal injury was still not clear. A recent study showed excessive activation of excitatory neurotransmitter-glutamate which played an important role in axonal injury. Our experiment focused on the mechanism of EAE and axonal injury by establishing animal model of EAE combined with drug intervention. To provide further theory foundation for mechanism of demyelinating disease and axonal injury, and to find new therapeutic ways in EAE by using of dizocilpine maleate (MK - 801 ) .Methods : Female SJL/J mice immunized with the p139-151 peptide of myelin proteolipid protein(PLP) and BCG vaccine in incomplete Freund's adjuvant developed EAE. PLP peptide antigen immunized sensitive SJL/J female mice, meanwhile received tail vein injection of Bordetella pertussis bacilli .After 7 days of immunization experimental mice received intervention of MK-801.We calculated neurological function score and weighted the mice daily. Mice were killed when the first neurological attack and their brains and spinal cords tissue samples were stripped , and stained with hematoxylin and eosin(HE), luxol fast blue(LFB), Bodian's silver stain impregnation. The primary antibodies for immunohistochemical staining were anti-APP, anti-myelin basic protein(MBP) and anti-glial fibrillary acidic protein(GFAP).Results : Seven(23.3%) mice attacked in 15～22 days after immunized. Average attack time was 19±2.58days. Average clinical neurological score was 2.14±0.69.The average weight was 21.85±0.94g before immunized and 23.24±1.55g after immunized(no significant difference). Drug treatment group (MK-801 0.30mg/kg ) mice: Five(16.7%) mice attack in 16～25 days after immunized. The average onset time was 21±1.25 day(sp< 0.05),. The average neurological score was 1.08±0.42(p< 0.02,compared with control group).Lesions showed that the incidence of vascular lesions when sheath formation, inflammatory cell infiltration and demyelination and axonal injury. Demyelinating were found with LFB stain, where axon was swellen and transection with Bodian's silver stain. APP-positive axons in active demyelinating lesions which MBP-positive and GFAP-negative.Drug treatment Group was unable to inhibit inflammatory cell infiltration,but APP-positive axons were decreased,That indicated axonal injury alleriated.Conclusion : The pathological changing of PLP_139-151 induced EAE mainly involved spinal cord. Axonal damage was found at disease onset before demyelinating, and not paralleled with the clinical symptoms in the early stage.The pathophysiological mechanism of axonal injury in early stage of EAE was dissimilar to demyelination itself. From our result Excitatory glutamate toxicity might be related with the pathogenesis of MS and axonal injury. NMDA receptor antagonist , MK - 801 ,could significantly inhibit neuvoue function deficits, reduce axonal injury and morbidity. Background and Objective To analyze the imaging characteristics of tumor-like inflammatory demyelinating diseases(TIDD). To evaluate the role of enhanced gadolinium DTPA magnetic resonance imaging(MRI) and diffusion weighted imaging(DWI) in the diagnosis and discrimination with TIDD.Methods 18 patients of TIDD were studied on MRI and/or CT scan.Results Lesions of all cases were showed hypointense signal on CT scan and T1 Weighted Imaging(T1WI) of MRI, but that were showed hyperintense signal on T2 Weighted Imaging(T2WI).Lesions could be enhanced by the method of Gd DPTA contrast. 56.3% of them were open-ring signs.Acute lesions were identified on DWI with hyperintense signal.Conclusions It is a difficult task to make the correct diagnosis of TIDD based on the clinical information and imaging findings,and this disease entity is often misdiagnosed as tumor by MRI. MRI technology played an important role in diagnosing and staging of TIDD. Thorough analysis of the clinical history and careful observation of MR manifestations (especially contrast enhanced MR findings) would be helpful in diagnosing the TIDD. Pathological test is the most valueable evidence for avoiding the devastating injury caused by surgery or radiation therapy.