This is a development and feasibility study of central nervous system (CNS) disease in a murine model of systemic lupus erythematosus (SLE). At present, the causes of CNS disease in SLE are largely unknown. Our ability to study the disease is limited by a lack of understanding of the basic pathogenic mechanisms underlying this form of lupus. Progress in this area has been delayed by the lack of an animal model of CNS lupus and by the absence of reliable measures of disease activity in the CNS. This proposal will evaluate magnetic resonance imaging (MRI) as a diagnostic tool for the assessment of CNS involvement in the NZB/NZW (B/W) lupus-prone mouse model. It is based upon the observations that individual have histopathologic abnormalities in discreet regions of the brain, and that similar individual B/W mice with advanced disease have abnormal magnetic resonance signals in the brain. It is therefore hypothesized that (MRI) can be used to accurately assess CNS disease in a murine model in vivo. The proposed work will establish the incidence and prevalence of MRI abnormalities in B/W mice and correlate their appearance with the development of other features of systemic autoimmunity. It will also determine the immunohistopathologic correlates of these abnormal MRI signals, and determine whether there is a correlation between MRI abnormalities and anticardiolipin antibody levels in these mice.
These aims will be accomplished by systematically studying a cohort of B/W mice using brain MRI during the course of the development of disease. By examining brain pathology by histology and immunohistochemistry in B/W mice both with and without abnormal brain MRI findings, and by measuring anticardiolipin antibodies in B/W mice both with and without abnormal brain MRI findings. Development of an in vivo method for assessing CNS lupus would provide the means for studying this disease in a well-established animal model of SLE, and for studying the effects of new therapeutic agents on CNS lupus in a preclinical model. These studies therefore have direct relevance to the understanding and treatment of human disease.
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