Opening of tight junctions in cerebral endothelium. I. Effect of hyperosmolar mannitol infused through the internal carotid artery.

Infusion of 1.8 M mannitol solution into the internal carotid artery of Wistar rats allows horseradish peroxidase (HRP) to cross cerebral vascular endothelium via intercellular pathways. This was made evident by density gradients of HRP observed in consecutive tight junctional compartments following in vivo administration, and by the passage of colloidal lanthanum through junctional membrane appositions of glutaraldehyde fixed cerebral endothelium. Three hours after mannitol infusion, small non-capillary vascular segments were still focally permeable to HRP. Twenty-four hours after the osmotic insult, the tracer was absent in the affected hemisphere. Water and electrolyte assays indicated absence of brain edema during the period of observation of blood-brain barrier opening.