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The Controversy Surrounding the Pathogenesis of the Multiple Sclerosis Lesion

      The main issues in multiple sclerosis research revolve around four fundamental questions. (1) What initiates the disease—that is, autoimmune T cells, a virus, or a toxin? (2) Is the inflammatory response primary to the development of demyelination, or is it a secondary response to injury? (3) Is the oligodendrocyte, the myelin-producing cell, the primary target? (4) How can myelin repair be promoted? This review focuses on the controversies revolving around these important questions. Although many investigators believe that T-cell receptors on CD4+ cells interact with myelin antigens to initiate an inflammatory cascade that leads to myelin destruction, others maintain that a viral agent may have a direct or indirect role in the pathogenesis of multiple sclerosis. The concept that the immune system contributes to the tissue destruction in multiple sclerosis is generally accepted; however, the debate about cause versus consequence of the pathologic process remains unresolved, as does the identification of the initial event or focus of the damage. Electron microscopic studies have disclosed evidence of remyelination (albeit often incomplete) in lesions of multiple sclerosis. Enhanced understanding of the factors limiting remyelination could help formulate strategies to promote repair. By innovative experimental design and application of available molecular techniques, the answers to these questions may provide insights on how to prevent or treat multiple sclerosis
      BBB (blood-brain barrier), CNS (central nervous system), CSF (cerebrospinal fluid), EAE (experimental autoimmune encephalitis), HHV-6 (human herpesvirus 6), HLA (human leukocyte antigen), IFN (interferon), IL (interleukin), MBP (myelin basic protein), MHC (major histocompatibility complex), MRI (magnetic resonance imaging), MS (multiple sclerosis), PLP (proteolipid protein), SCH (spinal cord homogenate), TCR (T-cell receptors), TGF (transforming growth factor), TMEV (Theiler's murine encephalomyelitis virus), TNF (tumor necrosis factor), V (variable)
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