Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions.
Infusion of hyperosmolar solutions into the internal carotid artery causes opening of blood-brain barrier to macromolecules. Ultrastructural tracer studies indicate that extravasation of macromolecules takes place primarily in segments of large penetrating cortical blood vessels. The purpose of the present study was to examine fracture faces of cerebral endothelium in normal and hyperosmolar mannitol-treated rat brains in an attempt to elucidate: (a) the organization of endothelial cell junctions in various segments of the cerebral vascular bed and (b) the structural basis of blood-brain barrier opening in hyperosmotic conditions. We found that in control rat brains: (a) capillary endothelium is provided with complex networks of continuous multistranded tight junctions; (b) continuous capillary-type tight junctions extend, although in a simpler beltlike fashion, into the endothelium of postcapillary venules; (c) the endothelium of collecting veins possess widely discontinuous single- or double-stranded tight junctions associated with gap junctions; (d) arteries have endothelial tight junctions containing focal discontinuities associated with gap junctions. In hyperosmolar mannitol-treated rat brains, there appeared focal distensions of compartments but no definitive structural discontinuities in capillary-type tight junctions. Our data suggest that the blood-brain barrier consists of: (a) an extended tight region (comprising both capillaries and postcapillary venules) and (b) focal, potentially leaky regions (restricted to collecting veins and possibly arteries). Our studies furnished no direct evidence for the structural basis of blood-brain barrier opening in hyperosmolar mannitol-treated rat brains.
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D002196:Capillaries / Q000648:ultrastructure; D002339:Carotid Arteries; D002536:Cerebral Arteries / Q000648:ultrastructure; D004727:Endothelium / Q000187:drug effects / Q000648:ultrastructure; D005614:Freeze Fracturing; D007365:Intercellular Junctions / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D014680:Veins / Q000648:ultrastructure; D014699:Venules / Q000648:ultrastructure
D008353:Mannitol