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1995-03-04
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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).