Cocaine opens the blood-brain barrier to HIV-1 invasion

Ling Zhang, David Looney, Dennis Taub, Sulie L. Chang, Dennis Way, Marlys H. Witte, Michael C. Graves, Milan Fiala

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Cocaine abuse has been associated with vasculitis and stroke, and is suspected to influence the progression of AIDS dementia. Cocaine may enhance HIV-1 neuroinvasion by actions directed at the blood-brain barrier. HIV-1 appears to penetrate the human brain microvascular endothelial cell barrier by a paracellular route breached by tumor necrosis factor-α (TNF-α). Cocaine's effects on the blood-brain barrier were investigated using human brain microvascular endothelial cells and peripheral blood monocytes. Cocaine (10-5 M and 10-6 M) increased molecular permeability of the barrier and viral invasion by the macrophage-tropic HIV-1(JR-FL) into the brain chamber. Cocaine also augmented apoptosis of brain endothelial cells and monocytes, increased secretion of four chemokines (interleukin-8, interferon-inducible protein-10, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1) and the cytokine, TNF-α, by human monocytes. TNF-α enhanced invasion of the brain compartment by macrophage-tropic, lymphotropic, and bitropic HIV-1 strains. These data indicate that HIV-1 neuroinvasion can be increased by (a) cocaine's direct effects on brain microvascular endothelial cells and (b) paracrine effects of cocaine-induced pro-inflammatory cytokines and chemokines on the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalJournal of NeuroVirology
Volume4
Issue number6
DOIs
StatePublished - Dec 1998

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Keywords

  • Apoptosis
  • Cocaine
  • Endothelial cells
  • HIV-1
  • Macrophage inflammatory protein-1α
  • Monocyte chemoattractant protein-1
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Cite this

Zhang, L., Looney, D., Taub, D., Chang, S. L., Way, D., Witte, M. H., Graves, M. C., & Fiala, M. (1998). Cocaine opens the blood-brain barrier to HIV-1 invasion. Journal of NeuroVirology, 4(6), 619-626. https://doi.org/10.3109/13550289809114228