Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) tat protein causes inflammation, gliosis, apoptosis, and ventricular enlargement

J Neuropathol Exp Neurol. 1998 Jun;57(6):563-70. doi: 10.1097/00005072-199806000-00004.

Abstract

To determine the role of the Tat protein of the human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was injected intraventricularly as a single or repeated dose into male Sprague-Dawley rats. Histopathological evaluation showed an initial infiltration of neutrophils one day after Tat injection, followed by macrophages and lymphocytes by 7 days. Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular enlargement 7 days following the last injection. Nuclear magnetic resonance spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that the transient extracellular exposure of the central nervous system to Tat protein of HIV can cause a cascade of events leading to the influx of inflammatory cells, glial cell activation, and neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Astrocytes / physiology
  • Basal Ganglia / chemistry
  • Basal Ganglia / immunology
  • Basal Ganglia / metabolism
  • Biotin
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / immunology
  • Cerebral Cortex / metabolism
  • Cerebral Ventricles / immunology
  • Cerebral Ventricles / pathology*
  • Encephalitis, Viral / immunology
  • Encephalitis, Viral / pathology
  • Ependyma / pathology
  • Gene Products, tat / pharmacology*
  • Gliosis / pathology*
  • Gliosis / virology
  • Glutamic Acid / analysis
  • HIV-1*
  • Hippocampus / chemistry
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Humans
  • Injections, Intraventricular
  • Magnetic Resonance Spectroscopy
  • Male
  • Neutrophils
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Staining and Labeling
  • gamma-Aminobutyric Acid / analysis
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • Recombinant Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Aspartic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Biotin
  • N-acetylaspartate