Development of laboratory and animal model systems for HIV-1 encephalitis and its associated dementia

Yuri Persidsky, Howard Eliot Gendelman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The neuropathogenesis of HIV-1 encephalitis and its associated dementia revolves around sustained viral replication in cells of mononuclear phagocyte origin (brain macrophages, multinucleated giant cells, and microglia). Macrophage secretory factors play important roles in facilitating monocyte trafficking into the brain, in regulating productive viral replication, and in producing neurotoxic responses. To study these events, we constructed an artificial blood-brain barrier (BBB) to assay monocyte transendothelial migration and developed an animal model system for HIV-1 encephalitis to ascertain the role that virus-infected mononuclear phagocytes play in disease pathogenesis. The BBB model was composed of brain microvascular endothelial cells and astrocytes placed on opposite sides of a porous membrane. Monocyte activation, not HIV-1 infection per se, was the central event affecting monocyte BBB migration. Many of the pathological features of HIV-1 encephalitis were reproduced in SCID mice stereotactically inoculated with virus-infected monocytes. These included widespread astrogliosis, apoptosis of neurons, dendritic damage, and macrophage/microglial activation. Such laboratory and animal model systems are being used to ascertain the pathogenic potential of virus-infected macrophages in brain and ways to curb such injurious effects.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalJournal of Leukocyte Biology
Volume62
Issue number1
DOIs
StatePublished - Jan 1 1997

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Encephalitis
Dementia
HIV-1
Monocytes
Animal Models
Blood-Brain Barrier
Macrophages
Brain
Phagocytes
Viruses
Transendothelial and Transepithelial Migration
Blood Substitutes
SCID Mice
Macrophage Activation
Microglia
Giant Cells
Astrocytes
HIV Infections
Endothelial Cells
Apoptosis

Keywords

  • Blood-brain barrier
  • Macrophage

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Development of laboratory and animal model systems for HIV-1 encephalitis and its associated dementia. / Persidsky, Yuri; Gendelman, Howard Eliot.

In: Journal of Leukocyte Biology, Vol. 62, No. 1, 01.01.1997, p. 100-106.

Research output: Contribution to journalArticle

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