Immunohistopathological changes in myelin oligodendrocyte glycoprotein 40-54 induced experimental autoimmune encephalomyelitis

GARAY L; GONZÁLEZ DENISELLE, M.C.; VILLA AM; GARCEA O; SICA REP; DE NICOLA A. F.

Thessaloniki, Grecia

Congreso; 21st Congress of the European Committee for the treatment and Research in Multiple Sclerosis. 10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.; 2005

European Committee for the treatment and Research in Multiple Sclerosis and Americas Committee for Treatment and Research in Multiple Sclerosis

Experimental autoimmune encephalomyelitis (EAE) is an induced immune inflammatory disease of the Central Nervous System (CNS) whose antigenic target is partly unknown. Most of its pathologic and clinical features resemble human Multiple Sclerosis. EAE may be induced with a number of myelin proteins, such as myelin basic protein, myelin oligodendrocyte glycoprotein (MOG), PLP and myelin associated-glycoprotein. Depending on the antigen employed, route of immunization and animal species, EAE may show different clinical manifestations, namely monophasic acute, progressive, relapsing/remitting or chronic. There are several reports of EAE induction in rodents employing the peptide MOG35-55. However, the demyelination pattern in rodents receiving pMOG40-54 is still missing. We studied the following parameters: a)Hematoxilin-Eosin staining and immunohistochemistry (IHC) for CD4, CD8, CD45 and ED1 to determine the type of cells infiltrating the compromised area, b)Luxol Fast Blue staining to assess the extent of the demyelination, c)IHC for glial fibrillary acidic protein (GFAP). Quantification was made using computer-assisted image analysis (OPTIMAS 6.02). Female C57/BL6 mice were immunized with pMOG40-54 (kind gift of D. Sun) emulsified in complete Freund?s adjuvant. Animals were clinically assessed daily and classified as suffering light, moderate and severe impairment. All of them developed an acute monophasic disease. We found a 7 fold increase in the number of GFAP+ astrocytes/mm2 in gray matter of the spinal cord in pMOG40-54+vs control (pMOG40-54+:152.7 ± 17.39 vs control:20.95 ± 8.37, p=0.0015). The density of GFAP+ cells (r=0.979, p<0.005) and the immune infiltration area (r=0.97 p=0.028) significantly increased when the clinical impairment augmented. A positive correlation between the extent of demyelination and the infiltrated area (r=0.99, p<0.0019) was demonstrated. The majority of the grouped immune cells were identified as ED1+ macrophages, with fewer isolated perivascular lymphocytes (CD8+, CD4+ or CD45+). Although other CNS regions were affected in this model as well, the spinal cord and the optic tract seemed to be mostly compromised. Therefore, the clinical-pathological studies of pMOG40-54 induced EAE may contribute to redefine a subtype of EAE and it might help to a better understanding of the effect of neuroprotectants acting on these disorders.