Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats

Aims/hypothesis. We undertook the characterization of the capillary bed of the rat frontal cortex and their permeability properties in short-term and long-term diabetic rats. Methods. Diabetes was induced by strepozotocin injection. Rats were maintained hyperglycaemic without insulin treatment during 4 to 5 months (short-term) and 8 to 13 months (long-term). Rats from an additional short-term hyperglycaemic group received an injection of exogenous dinitrophenylated albumin 15 min before being killed. Tissues were processed for electron microscopy and quantitative immunocytochemistry. Endogenous and dinitrophenylated exogenous albumin were revealed with high resolution over the capillary wall using specific antibodies and the protein A-gold complex. Morphometrical analyses were carried out. Results. Albumin is transported across endothelial cells by plasmalemmal vesicles or caveolae and larger vacuolar structures. This transport increased in diabetic rats by an increment in the number of vesicles. Albumin distribution across the capillary basement membrane showed that the restrictive properties of the basement membrane present in normoglycaemic rats are altered in the diabetic condition, as was its thickness. Similar alterations of the basement membrane structure and function were encountered in old normoglycaemic rats but to a lesser extent. Conclusion/interpretation. The results indicate that diabetes seems to accelerate the ageing process of the vascular wall and that the central nervous system capillary bed is also a target for diabetic microangiopathy.