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Cerebrovascular Permeability in the Normal Brain and Following Osmotic Opening of the Blood-Brain Barrier

  • Stanley I. Rapoport

Summary

Cerebrovascular permeability of nonelectrolytes and organic electrolytes is directly proportional to the octanol/water partition coefficient of these substances, as was determined by a new method of compartmental analysis which is sufficiently sensitive to examine permeability coefficients as low as 10−8 cm sec−1 (i.e., sucrose permeability) or as high as 10−4 cm sec−1 (i.e., antipyrine and caffeine permeabilities). In the latter case, cerebral blood flow must be taken into account to correct for extraction of tracer during its passage through the brain. The compartmental analysis method was employed in conscious rats, when radiotracer was injected i.v. as a bolus and tracer entry into the brain was analyzed in terms of a permeability coefficient and cerebral distribution volume. The proportionality between cerebrovascular permeability and octanol/water partition coefficient suggests that substances enter the brain by dissolving in the lipoid membranes of the continuous cerebrovascular endothelium (blood-brain barrier) and not by passing through aqueous pores within the endothelium. In order to overcome permeability limitations to intravascular water-soluble compounds, furthermore, it is possible to open the blood-brain barrier by infusing, into the carotid artery, a hypertonic solution of a water-soluble solute such as arabinose. Physiological and ultrastructural evidence indicates that osmotic opening of the blood-brain barrier is mediated by widening of tight junctions between cerebrovascular endothelial cells. In the rat, osmotic barrier opening occurs abruptly at a threshold arabinose concentration of 1.6 molal, and at an infusion time of 20 sec. 14C-sucrose permeability is increased 10–20 fold by osmotic treatment, but the increase disappears within about 1 hr. Brain edema and stimulation of cerebral glucose consumption follow osmotic treatment, and also disappear without resultant evidence of long-term brain damage. Osmotic barrier opening has proven useful for allowing normally-excluded substances into the brain.

Keywords

Tight Junction Lipid Solubility Hypertonic Solution Carbamate Ethyl Barrier Opening 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Stanley I. Rapoport
    • 1
  1. 1.Laboratory of Neurosciences National Institute on Aging, Gerontology Research CenterBaltimore City HospitalsBaltimoreUSA

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