Cellular mechanisms of the blood-brain barrier (BBB) opening to albumin-gold complex

Abstract

Cold lesion injury applied to mouse brain and infusion of hyperosmolar L(+) arabinose solution into rat carotid artery were used as extravascular and intravascular insults, respectively, leading to blood-brain barrier (BBB) disruption. To study the cellular mechanisms of the BBB opening, heterologous (bovine) and homologous (mouse and rat) albumin-gold complexes were used as a macromolecular tracer. Both insults rapidly induce the leakage of the blood-borne tracer, although the mechanisms of their action appear to be different. Cold lesion injury (cryoinjury) leads to the opening of interendothelial junctions and concomitantly to an endothelial-platelet reaction. This insult is followed by irreversible changes such as desquamation, degeneration and necrosis of the endothelial lining, formation of thromboses, and disruption of the basement membrane. Osmotic opening occurs through at least the four mechanisms (presumably temporal and reversible) that follow: 1) opening of a part of the junctional complexes; 2) the formation of transendothelial openings (interendothelial gaps or penetrating, crater-like excavations); 3) the uncontrolled passage of tracer particles through the cytoplasm of the injured endothelial cells; and 4) segmental denudation of the endothelial lining. The basement membrane appears to represent one of the main obstacles in the passage of blood-borne albumin-gold complexes to the extracellular space in the brain parenchyma.