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Drug Transfer Across the Blood-Brain Barrier: Correlation Between in Vitro and in Vivo Models

  • M. P. Dehouck
  • B. Dehouck
  • J. C. Fruchart
  • R. Cecchelli
  • P. Jolliet-Riant
  • F. Bree
  • J. P. Tillement
Part of the NATO ASI Series book series (NSSA, volume 257)

Abstract

To provide an in vitro system for studying brain capillary functions, we have developed a process of co-culture that closely mimics the in vivo situation, by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. In these conditions, endothelial cells retain all the endothelial cell markers and the characteristics of the blood-brain barrier. To validate our in vitro blood-brain barrier model, we have compared the transport of ten different compounds across the in vitro model vs. transport across the blood-brain barrier in vivo. In vivo brain extraction (Eo) are measured according to the method of Oldendorf. The in vivo and in vitro Eo values show a strong correlation as indicated by the Spearman’s co-efficient (r = 0.88, p < 0.01). The in vitro blood-brain barrier permeability for glucose and leucine i.e. compounds that traverse the blood-brain barrier via carrier mediation is in the same range as the blood-brain barrier permeability in vivo indicating that in our model the glucose and leucine transporters are always present. The relative ease with which such co-cultures can be produced in large quantities would facilitate the investigations in delivery of nutriments across the blood-brain barrier, and the screening of new centrally acting drugs.

Keywords

Public Health Endothelial Cell Strong Correlation Brain Barrier Relative Ease 
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.

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • M. P. Dehouck
    • 1
  • B. Dehouck
    • 1
  • J. C. Fruchart
    • 1
  • R. Cecchelli
    • 1
  • P. Jolliet-Riant
    • 2
  • F. Bree
    • 1
  • J. P. Tillement
    • 1
  1. 1.U325 Institut Pasteur de LilleLille CédexFrance
  2. 2.Laboratoire Hospitalo-Universitaire de Pharmacologie UFR de Médecine de Paris XIICréteilFrance

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