Pathological examination of the affected human tissue is key to understanding the possible mechanisms
operating in the disease. In multiple sclerosis (MS), studies of central nervous system (CNS) tissues reveal the
inflammatory nature of the disease associated with demyelination and axonal damage. Based on the concept of a
pathogenic adaptive immune response, immunosuppressive therapies have been developed in an attempt to block or
inhibit the potentially pathogenic T and B cells. More recently, re-examination of the neuropathology has led to a
resurgence of interest in the neurodegenerative aspects of the disease, the involvement of cortical damage as well as the
role of innate immunity in MS. These ideas have led to paradigm shifts from MS being the result of autoimmunity to
myelin due to initial adaptive immune responses, to that of a neurodegenerative disease in which, besides T and B cells,
innate immunity may play a major role in the disease process. The neuropathological studies have undoubtedly influenced
pharmaceutical interest in development of neuroprotective approaches. Here we review the latest findings from
pathological studies of MS tissues and discuss the relevance of these findings for future therapeutic approaches.
Keywords: Multiple sclerosis, demyelination, inflammation, neurodegeneration, preactive lesions.
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