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.
Brown
Rachel C
RC
Department of Pharmacology, The University of Arizona, College of Medicine, PO Box 24-5050, 1501 N. Campbell Ave., Tucson, AZ 85724, USA.
Egleton
Richard D
RD
Davis
Thomas P
TP
D000418:Albumins / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005070:Evans Blue / Q000493:pharmacokinetics; D005260:Female; D008353:Mannitol / Q000494:pharmacology*; D008636:Mesencephalon / Q000378:metabolism*; D008970:Molecular Weight; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D013395:Sucrose / Q000493:pharmacokinetics*
D000418:Albumins; D015415:Biomarkers; D012414:Rubidium Radioisotopes; D008353:Mannitol; D005070:Evans Blue; D013395:Sucrose