Mannitol opening of the blood-brain barrier:: regional variation in the permeability of sucrose, but not 86Rb+ or albumin

Clinically, infusion of hyperosinolar solutions is used to enhance chemotherapeutic drug penetration of the blood-brain barrier (BBB) in patients with malignant brain tumors or metastases. We examined the effect of hyperosmolar BBB disruption on brain permeability of three compounds, R-86(+), a marker for K+ permeability and transport, [C-14] sucrose and Evans blue albumin, using a rat in situ perfusion model. Rb-86(+) and [C-14] sucrose had increased permeability 20 min after BBB disruption with 1.6 M mannitol. There was no change in Evans blue albumin permeability. Only [C-14] sucrose showed regional variation in permeability after mannitol-induced BBB disruption, with the cortex and midbrain having higher sucrose permeability then either the cerebellum or brainstem. These data suggest that the clinical efficacy of 9 hyperosmolar disruption therapy in conjunction with chemotherapeutic agents, of a similar molecular weight to sucrose, may be affected by the location of the tumor within the brain. (C) 2004 Elsevier B.V. All rights reserved.