The central hypothesis of this project application is that the pathogenesis of HIV encephalopathy may involve either direct mechanisms in which highly restricted HIV infections of glial or neurons lead to neural dysfunction, or indirect mechanisms in which infected microglial cells produce viral proteins or cytokines which in turn act on glial or neurons leading to dysfunction. This Core explores these hypotheses by studies of the brains of patients dying with AIDS. These brains will be used for two purposes, (i) histological based studies to compare the cellular distribution of HIV and cytokines with pathological lesions and (ii) as a tissue bank to support studies under other projects in this program. (i) Tissue bank. About 10 brains will be collected each year under aegis of the autopsy service at the Hospital of the University of Pennsylvania. These brains will constitute a tissue bank, with tissues stored in various ways to optimize them as a resource for other projects under this program, including virus isolation, PCR amplification of gene sequences, and histological section based studies of viral genomes, viral antigens, cellular markers, cytokine proteins, cytokine mRNAs, and standard neuropathological stains. (ii) Neuropathological mapping. Selected brains will be used to map the distribution of neuropathological lesion, distribution of HIV genomes by in situ PCR, HIV antigen by immunohistochemistry, and mRNAs by in situ hybridization for selected cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF).
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