Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinose

Hyperosmotic media infused into the cerebral circulation open the blood-brain barrier to protein and colloid. The mechanism whereby such substances cross the affected vessels is still disputed. We describe here the transendothelial route taken by ionic lanthanum (La3+), a small electron-dense tracer which, unlike colloidal lanthanum, can be administered to the living animal. In adult rats, 2.9 ml of hyperosmotic (1.4 M) arabinose was infused into the internal carotid artery as a 30-s bolus, followed by 5 mM LaCl3. To find the extravasated La3+, which is invisible by light microscopy, horseradish peroxidase (HRP) was injected simultaneously into the femoral vein. The hyperosmotic treatment resulted in exudation of both HRP and La3+ primarily around cerebral arterioles. The La3+ crossed arterioles through successive tight junctions between endothelial cells. Although the tight junctions were not discernibly opened, they must have become permeable because the extracellular pools between successive tight junctions were penetrated by the La3+. These pools are normally inaccessible to La3+. Luminal and abluminal pits and cytoplasmic vesicles, some of them containing La3+, formed intraendothelial clusters. Their role, if any, in the transfer of ion remains uncertain.