The pathology of multiple sclerosis and its evolution

Abstract

The pathology of multiple sclerosis (MS) was de¢ned more than a century ago as a chronic in£ammatory process which is associated with widespread primary demyelination and glial scarring. In this short review we discuss controversial issues on (i) the relationship between in£ammation and demyelination, (ii) the various possible mechanisms of myelin destruction, and (iii) axonal involvement in this disease. We suggest that the disease process of MS is more complex that previously believed.

Route of Uptake of Palmitoylated Encephalitogenic Peptides of Myelin Proteolipid Protein by Antigen-Presenting Cells: Importance of the Type of Bond between Lipid Chain and Peptide and Relevance to Autoimmunity

“…In contrast, N-P12 peptide did not dissociate but formed excimers or remained in a micellar form over the course of 24 h, as indicated by the green fluorescence. APC, since they are the most abundant APC type present in the EAE or MS lesion at the time of demyelination, when thiopalmitoylated peptides are likely to be released and taken up by APC (13). In addition, previous studies have shown that myelin-debrisladen macrophages from the CNS can travel to the CNS-draining lymph nodes and present myelin Ag to T cells (14 -16).…”

“…In the current study, we first compared the uptake of 100 M of biotinylated S-palm PLP 139 -151 , N-palm PLP 139 -151 , or nonpalmitoylated PLP 139 -151 into SJL/J peritoneal macrophages. Macrophages were used in this study, as they are the predominant APC type in the CNS during EAE and MS (13), and it has been shown that they are very efficient at taking up myelin breakdown products, transporting them to the deep cervical lymph nodes, and presenting these Ags to effector T cells (14 -16). They can also present Ag to naive T cells, but to a lesser extent than dendritic cells (16).…”

IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis

“…One of the more recent diseases treated with IFN-␤ is multiple sclerosis (MS). 3 MS is considered an autoimmune disease characterized by inflammation and demyelination of the CNS leading to chronic neurologic disturbances (5,6). One of the most commonly used therapies for MS at present is systemic administration of IFN-␤.…”

Identification of Genetic Loci Controlling the Characteristics and Severity of Brain and Spinal Cord Lesions in Experimental Allergic Encephalomyelitis

“…Different immunological pathways including, but not limited to, cytotoxic cytokines, demyelinating antibodies, cell-mediated cytotoxicity, and apoptosis may be responsible for the different patterns of demyelination. [11][12][13] Although the pattern of demyelination is heterogenous between patients, lesions within the same patient tend to be homogenous, suggesting that different mechanisms of demyelination may operate in different patient subgroups, perhaps reflecting an underlying genetic influence. [11][12][13] In addition to the differences in lesion type, variation is seen in the location of MS lesions.…”

“…[11][12][13] Although the pattern of demyelination is heterogenous between patients, lesions within the same patient tend to be homogenous, suggesting that different mechanisms of demyelination may operate in different patient subgroups, perhaps reflecting an underlying genetic influence. [11][12][13] In addition to the differences in lesion type, variation is seen in the location of MS lesions. 14 Patients with primarily progressive MS often exhibit lesions in the spinal cord (SC) without cerebral involvement.…”