Enhanced Diagnostic Tools
Multiple sclerosis (MS) is an inflammatory, demyelinating diseaseof the central nervous system (CNS). It affects approximately 0.4 million Americans between the ages of 20-40 years. MS syndrome has been suggested to arise from multiple pathogenic pathways, due to the variation in the clinical signs and disease course diagnosed among individuals.Mechanistic insights into the complex pathogenesisof MS have relied extensively on animal models of CNS demyelination.One of the most commonly models used to study MS is Encephalomyelitis (EAE).
EAE is induced by stimulating an immune responsedirected against CNS antigens.Active induction of EAEis accomplished by immunization with myelin antigens emulsified in adjuvant.Multiple sclerosis is considered to be Th1-mediatedautoimmune diseases in which neuroantigen-reactive lymphocytes infiltratethe CNS, mediate the developmentof inflammatory lesions, and insome models, trigger the demyelinationof axons leading to progressive paralysis. Elevatedlevels of IL-12 have been reported in humans with progressive multiple sclerosis. Increased frequencies of IL-12–secretingmonocytes appear to correlatewith active brain lesions detected by magnetic resonance imaging. IL-12 has been functionally implicatedin the development of EAE bythe observations that αIL-12 (αp70)blocks disease development in miceand IL-12 p40–/– mice are resistant toEAE induction.
Experimental autoimmune encephalomyelitis (EAE) can be induced in SJL mice by immunization with proteolipid protein (PLP), myelin basic protein (MBP), or peptides. Peptides used correspond to the immunodominant epitopes of MBP (MBP84-104), MOG (MOG92-106), or PLP (PLP139-151 and PLP178-191). In C57BL/6 mice the disease can be induced by immunization with the peptide corresponding to the immunodominant epitope of MOG (MOG35-55).
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