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.