Pathological findings in rats with experimental allergic encephalomyelitis

作者:Dong Mei; Liu Ruichun; Guo Li; Li Chunyan*; Tan Guojun
来源:Acta Pathologica, Microbiologica et Immunologica Scandinavica, 2008, 116(11): 972-984.
DOI:10.1111/j.1600-0463.2008.00726.x

摘要

The aim of this study was to establish an animal model of experimental allergic encephalomyelitis (EAE) and examine the basic pathological changes, as well as expression and distribution of MMP-2 and MMP-9, in Wistar rats. Tissue sections were processed for HE staining, Weil myelin staining, and modified Bielschowsky staining. Expression and distribution of glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were detected with immunohistochemistry. We divided the EAE into five types, depending on pathological characteristics and clinical manifestations: acute EAE, relapsing-remitting EAE, progressive EAE, benign EAE, and asymptomatic EAE. Rats with acute EAE suffered from quick, severe attacks with widespread inflammatory cells and axonal loss. No demyelination or astrocytic hyperplasia was found around the lesions. Rats with relapsing-remitting EAE broke down twice, with many perivascular cuffs and demyelinating plaques in lesions; hyperplastic and hypertrophic astrocytes characterized old lesions and axonal loss was evident. Rats suffering from progressive EAE exhibited continuous aggravation without improvement, accompanied by perivascular cuffs, demyelination, increased gliocytes and axonal damage. Rats with benign EAE recovered to a normal state with obviously decreased inflammatory cells and almost entirely unaffected myelin and axons. Rats with asymptomatic EAE also had various pathological changes that were not coincident with their clinical manifestations. Elevated expression of MMP-2 and MMP-9 was concordant in different types of EAE, but the extent differed in each type of EAE. MMP-2 and MMP-9 can be expressed in the form of vascular endothelial cells, meninges, or accumulated inflammatory cells. Multiple clinical courses of disease were demonstrated in Wistar rat EAE, with attributes similar to multiple sclerosis (MS) in clinical and pathological characteristics. Elevated expression of MMP-2 and MMP-9 may play a role in some aspects of pathological changes in EAE, for example, destroying the blood-brain barrier, degrading the myelin sheath, and damaging axons.