This Research Center will investigate the clinical manifestations, cellular pathology, and pathogenetic mechanisms of the neurological complications of HIV infections in humans. In addition, animal models will be developed to provide insights into the pathogenesis f neural lesions. Cohorts of persons infected by different routes, including gay men, intravenous drug users, and infants of HIV- positive mothers, will be studied prospectively to determine the frequency, spectrum and course of central and peripheral nervous system complications. This longitudinal data along with cross- sectional clinical data on patients with AIDS will provide the base for morphological, imaging, and immunological studies. Cellular pathology will be defined with a variety of morphological methods with emphasis on delineating the peripheral nerve abnormalities, the involvement of the dorsal root and autonomic ganglia, and the cellular pathology of the vacuolar myelopathy and HIV encephalopathy. This encephalopathy will be studied during life using quantitative MRI and single photon emission computed tomography (SPECT) methods and post-mortem with morphometric analysis. Selective or diffuse neuronal loss and the basis of the diffuse myelin pallor will be studied. The phenotype of inflammatory cells, their state of activation and presence and localization of cytokines in nervous system tissue will be correlated with localization of viral antigens and RNA; conversely, the effect of HIV infection on macrophage function and monokine production will be examined. Transgenic mice containing specific and the possible role of gene products in nervous system pathology. The pathogenesis of the neurological involvement with feline immunodeficiency lentivirus will be investigated as a practical animal model for the neurological complications of HIV infection.
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