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

Objective: To verify whether HIV envelope protein gp120 changes the blood-b rain barrier in vivo, as a fundamental mechanism of early central nervous s ystem damage by HIV-1. Design: Analysis of the functional integrity and immune activation of the b lood-brain barrier in brains of HIV-1 gp120 transgenic mice secreting circu lating gp120 at levels similar to those detected in AIDS patients. Methods: Number of vessels/mm(2) section area with perivascular albumin and percentage of vessels expressing adhesion molecules (ICAM-1 and VCAM-1) we re determined by immunohistochemistry in frozen brains from autopsied trans genic and non-transgenic mice. The percentage of vessels showing substance P immunoreactivity was also calculated, as this neuropeptide is known to me diate the increase in permeability of the rat brain endothelium in vitro ca used 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 great er percentage of ICAM-1- and VCAM-1-positive brain vessels in transgenic th an 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 perc entage of substance P-positive and ICAM-1-positive brain vessels (P < 0.000 1) in transgenic mice. Conclusions: These findings demonstrate that HIV-1 gp120 is capable of chan ging and activating in vivo the vascular component of the blood-brain barri er. (C) 1999 Lippincott Williams & Wilkins.