X-Message-Number: 11885
Date: Fri, 4 Jun 1999 06:28:00 -0700 (PDT)
From: Doug Skrecky <>
Subject: blood-brain barrier transport

  Lucchesi KJ.  Gosselin RE.
  Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover,
  New Hampshire 03756.
  Mechanism of L-glucose,
  raffinose, and inulin transport across intact blood-brain
  American Journal of Physiology.  258(3 Pt 2):H695-705, 1990 Mar.
  Brain capillary permeability-surface area products (PS) of hydrophilic
  solutes were evaluated in terms of a conventional two-compartment model. In
  rats whose blood-brain barrier (BBB) was presumed to be intact, metabolically
  inert carbohydrates with different molecular weights were injected in pairs
  to elucidate whether their transfer into the brain proceeds by diffusion
  through water- or lipid-filled channels or by vesicular transport. The
  distribution volume of 70 kDa dextran 10 min after intravenous injection was
  used as a measure of the residual volume of plasma in brain tissue after
  death. The two-compartment model yielded larger PS values for inulin and
  raffinose than for L-glucose, and the PS
  values of inulin and L-glucose were found to decrease as the labeling time
  was lengthened (10, 30, and 60 min). These observations were interpreted to
  mean that a rapidly equilibrating compartment was present between blood and
  brain, rendering the two-compartment model inadequate for computing true
  transfer rate constants. When multiple-time uptake data were reanalyzed using
  the three-compartment graphical analysis of Patlak, Blasberg, and
  Fenstermacher (J. Cereb. Blood Flow Metab. 3: 1-7, 1983), solutes of
  differing molecular size were found to enter the brain at approximately equal
  rates. This observation suggested that the predominant transport
  mechanism across an intact BBB is vesicular. Specifically,
  unidirectional transport is likely to be initiated by solute binding to the
  glycocalyx on the luminal surface of brain capillary endothelium. Apparently
  more inulin than L-glucose is absorbed, which may account for its slightly
  faster transfer across the BBB. We suggest that this adsorptive surface is
  the location of the rapidly equilibrating compartment on the plasma side of
  the BBB.

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