Document 0147 DOCN M9550147 TI In vivo model of HIV infection of the human brain. DT 9505 AU Achim CL; Miners DK; Burrola PG; Martin FC; Wiley CA; University of Pittsburgh Medical Center, Division of; Neuropathology, Pa. SO Dev Neurosci. 1993;15(6):423-32. Unique Identifier : AIDSLINE MED/95136894 AB Approximately one quarter of the AIDS patients have severe HIV encephalitis with diffuse neuronal damage that may be mediated by immune factors secreted by CNS macrophages. Based on an in vitro brain microsphere model, we developed an in vivo system in which human embryonic brain tissue survives for several months in the interscapular fat pad of SCID mice. Coculture of human brain tissue with macrophages prior to transplantation resulted in infiltration of the microspheres by activated macrophages. When the macrophages were infected in vitro with a neurotropic HIV strain, viral particles were detected in vivo up to 3 months after transplantation. HIV-infected transplants contained multinucleated giant cells similar to those seen in HIV encephalitis. However, the neuroglial component degenerated in the fat pad of SCID mice. The absence of synaptogenesis in the human transplants suggests that the murine fat pad lacks adequate stimuli or support for human neuronal differentiation. To study neurologic damage associated with HIV infection, sites of implantation that stimulate synaptogenesis (e.g. murine CNS) will need to be explored. Based on these findings we conclude that transplantation of brain microspheres with HIV-infected macrophages into SCID mice may be an achievable model of HIV encephalitis. DE Animal AIDS Dementia Complex/*PATHOLOGY/VIROLOGY Brain/*PATHOLOGY/VIROLOGY Brain Tissue Transplantation Cell Transplantation Cells, Cultured Fetal Tissue Transplantation Human Immunohistochemistry Macrophages/IMMUNOLOGY Male Mice Mice, SCID Microscopy, Electron Microspheres Models, Biological Nerve Degeneration Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transplantation, Heterologous JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).