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The blood-CSF barrier explained: when development is not immaturity

Pia A Johansson1, Katarzyna M Dziegielewska, Shane A Liddelow

  • 1Department of Pharmacology, University of Melbourne, Parkville, Vic, Australia. piaaj@unimelb.edu.au

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|February 23, 2008
PubMed

Insights

The developmental blood-CSF barrier is mature early on, restricting molecules via tight junctions. Protein and marker transfer occurs transcellularly, not via paracellular routes, explaining developmental changes in fetal brain barrier function.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Physiology

Background:

  • The maturity of brain barriers during development is debated.
  • High fetal cerebrospinal fluid (CSF) protein and decreasing marker permeability suggest immaturity.
  • Teleological interpretations and experimental data inform this debate.

Purpose of the Study:

  • To investigate the mechanism of the developmental blood-CSF barrier.
  • To determine if tight junctions mature early in development.
  • To explain the observed changes in CSF protein and marker permeability during development.

Main Methods:

  • Analysis of tight junction function in the blood-CSF barrier.
  • Assessment of transcellular vs. paracellular transport routes.
  • Modeling of volume of distribution effects on marker permeability.
  • Investigation of developmentally regulated cellular transfer mechanisms.

Main Results:

  • The blood-CSF barrier utilizes tight junctions, similar to adults, restricting paracellular passage of lipid-insoluble molecules.
  • Both proteins and passive markers are transferred via a transcellular route.
  • Decreased apparent permeability for passive markers is explained by changes in volume of distribution.
  • Developmentally regulated cellular transfer explains altered CSF protein concentrations.
  • Blood-CSF tight junctions are functionally mature early in development.

Conclusions:

  • The developmental blood-CSF barrier is functionally mature early, employing tight junctions.
  • Transcellular transport, not paracellular, is the primary route for molecules across the barrier.
  • Observed developmental changes in permeability and protein concentration are explained by cellular transfer and distribution volumes.

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