Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat

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Abstract
Vascular permeability P in different cerebral regions of the conscious rat was determined, independently of blood flow, for 14C tracers of glycerol, mannitol, sucrose, and inulin. A tracer was injected i.v., arterial plasma concentrations were monitored, and regional brain concentrations were measured at specific times thereafter. A plasma-brain 2-compartment model was used to calculate mean regional values of P, letting capillary area equal 240 cm2 .cntdot. g-1. P was 2-4 .times. 10-6 cm .cntdot. s-1 for glycerol, 0.95-1.4 .times. 10-7 for mannitol, 2.5-3.0 .times. 10-8 for sucrose, and 1.0-1.4 .times. 10-9 for inulin. Cerebrovascular permeability coefficients correspond to coefficients at single cell membranes and lipid bilayers, but are 1000 times less than at muscle capillaries. The relation between cerebrovascular permeability and octanol/water partition suggests that saccharides diffuse into the brain through homogeneous endothelial cell membranes and not through capillary pores or by means of vesicles. Estimated cerebral distribution volumes for the tracers indicate that glycerol distributes rapidly within the brain extracellular and intracellular compartments and may be incorporated into the metabolic pool, that mannitol distributes extracellularly and partially intracellularly, and that sucrose remains within the extracellular space.

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