Hydrophilic solute transport across the rat blood-brain barrier
Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB) was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.
- Research Organization:
- Dartmouth Coll., Hanover, NH (United States)
- OSTI ID:
- 5604344
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Comparison of various methods for delivering radiolabeled monoclonal antibody to normal rat brain
Differential blood-brain barrier permeabilities to (/sup 14/C)sucrose and (/sup 3/H)inulin after osmotic opening in the rat
Related Subjects
BLOOD-BRAIN BARRIER
PERMEABILITY
GLUCOSE
MEMBRANE TRANSPORT
INULIN
CARBON 14 COMPOUNDS
CELL MEMBRANES
MATHEMATICAL MODELS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALDEHYDES
CARBOHYDRATES
CARBON COMPOUNDS
CELL CONSTITUENTS
HEXOSES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MEMBRANES
MONOSACCHARIDES
ORGANIC COMPOUNDS
POLYSACCHARIDES
SACCHARIDES
550501* - Metabolism- Tracer Techniques