Evidence of blood-brain barrier alteration and activation... : AIDS (original) (raw)

Basic Science: Original Papers

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

Toneatto, Silvia; Finco, Orettaa; van der Putten, Hermanb; Abrignani, Sergioa; Annunziata, Pasquale

From the Institute of Neurological Sciences, University of Siena, aIRIS, Chiron SpA, Siena, Italy, and the bDepartment of Central Nervous System, Novartis, Basel, Switzerland.

Sponsorship: Supported by grants (n. 9304-05 and 9403-06) from the Italian Ministry of Health (Istituto Superiore di Sanità) AIDS Project to P.A.

Requests for reprints to: P. Annunziata, Istituto di Scienze Neurologiche, Università di Siena, Viale Bracci 2, 53100 Siena, Italy.

Received: 9 February 1999; revised: 14 July 1999; accepted: 23 September 1999.

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.