Effect of procyanidolic oligomers on the permeability of the blood-brain barrier

Blood-brain barrier (BBB) is the site of regulatory mechanisms which contro l the exchange of substances between the brain and the blood through the wa ll of 'true' brain capillaries with tight junctions between endothelial cel ls, in some pathological situations the permeability of the BBB is increase d because of a partial proteolytic degradation of some constituents of the capillary basement lamina. In such cases it is important to restore normal permeability. The effect of procyanidolic oligomers (PCO) on the BBB was in vestigated in vivo with quantitative morphologic procedures. We also invest igated the action of this drug on collagen and basement lamina constituents (Matrigel (R)) in vitro. Collagenase injected in lateral brain Ventricles was shown to increase BBB permeability. Per os administration of PCO to rat s greatly increased the resistance of brain capillaries to bacterial collag enase, as shown by the inhibition of the diffusion of fluorescein-isothiocy anate-marked dextran particles from the blood-stream into the brain tissues . Calf skin collagen pretreated in vitro with PCO became more resistant to the hydrolytic action of collagenase. Similar, even more intense protective effect was seen when basal lamina constituents containing type IV collagen was incubated with PCO before exposure to pronase. These in vitro effects may partly explain the in vivo protective effect of PCO against the alterat ion of brain capillaries by i.v. injected bacterial collagenase. (C) 2001 E ditions scientifiques et medicales Elsevier SAS.