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

Clinically, infusion of hyperosmolar 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, ⁸⁶Rb⁺, a marker for K⁺ permeability and transport, [¹⁴C]sucrose and Evans blue albumin, using a rat in situ perfusion model. ⁸⁶Rb⁺ and [¹⁴C]sucrose had increased permeability 20 min after BBB disruption with 1.6 M mannitol. There was no change in Evans blue albumin permeability. Only [¹⁴C]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 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.