Evidence of blood-brain barrier alteration and activation in HIV-1 gp120 transgenic mice

AIDS. 1999 Dec 3;13(17):2343-8. doi: 10.1097/00002030-199912030-00005.

Abstract

Objective: To verify whether HIV envelope protein gp120 changes the blood-brain barrier in vivo, as a fundamental mechanism of early central nervous system damage by HIV-1.

Design: Analysis of the functional integrity and immune activation of the blood-brain barrier in brains of HIV-1 gp120 transgenic mice secreting circulating gp120 at levels similar to those detected in AIDS patients.

Methods: Number of vessels/mm2 section area with perivascular albumin and percentage of vessels expressing adhesion molecules (ICAM-1 and VCAM-1) were determined by immunohistochemistry in frozen brains from autopsied transgenic and non-transgenic mice. The percentage of vessels showing substance P immunoreactivity was also calculated, as this neuropeptide is known to mediate the increase in permeability of the rat brain endothelium in vitro caused by HIV-1 gp120.

Results: The number of vessels with albumin extravasation was significantly higher in transgenic than non-transgenic mice brains (P = 0.0003). A greater percentage of ICAM-1- and VCAM-1-positive brain vessels in transgenic than non-transgenic mice was shown (P = 0.0017 and P = 0.0008 respectively). Significant immunoreactivity for substance P was detected in brain vessels in transgenic mice and a significant correlation was found between the percentage of substance P-positive and ICAM-1-positive brain vessels (P < 0.0001) in transgenic mice.

Conclusions: These findings demonstrate that HIV-1 gp120 is capable of changing and activating in vivo the vascular component of the blood-brain barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / physiology*
  • HIV Envelope Protein gp120 / genetics*
  • HIV Infections / immunology
  • HIV Infections / physiopathology*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity*
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Rats
  • Substance P / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • HIV Envelope Protein gp120
  • RNA, Messenger
  • RNA, Viral
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Substance P