Short (or topical) review
Is the pial microvessel a good model for blood-brain barrier studies?

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Abstract

Pial microvessels have commonly been used as model systems for studying blood-brain barrier (BBB) properties instead of cerebral cortical microvessels. Since pial microvessels are relatively accessible they have been especially employed in electrophysiological and pharmacological studies. Measurements of electrical resistance across endothelial cells (EC) as a measure of their barrier properties have been made exclusively from pial microvessels in in vivo BBB studies. Similarly the observed responses of microvessels to the application of pharmacological agents have commonly been made on pial microvessels as representative of BBB vasculature. In this review the properties of pial and cerebral microvessels are compared to determine whether the use of the pial microvessel as a model for BBB studies is valid. Similarities are described in their ultrastructural features, permeability to electron dense tracers and molecular characteristics. Measurements of electrical resistance from pial microvessels are compared with measurements from cerebral EC monolayers in tissue culture and indirect determinations for cerebral microvessels in situ. Two notable differences between pial and cerebral microvessels are described in the adult nervous system. Tight junctions between cerebral EC appear to consist of a uniform population. In pial microvessels however tight junctions consist of two populations, in one the inter-EC tight junctions resemble those between cerebral EC, with fusion of adjacent EC membranes. In the second population the inter-EC tight junctions differ with a discernible gap between adjacent EC membranes. The distribution of the endothelial barrier antigen (EBA) is uniform between EC of cerebral microvessels. By contrast EC of pial microvessels form a heterogeneous population for EBA expression which is related to the proximity of the EC to the astrocytic glia limitans. The role of astrocytes in the induction and maintenance of the BBB characteristics is briefly reviewed. The possible significance of the lack of an astrocytic ensheathment of pial microvessels is assessed. In summary, caution is urged in employing pial microvessels in BBB studies and the need for more information on possible pial microvessel heterogeneity is stressed.

References (78)

  • M.L. MacKenzie et al.

    Nodes of Ranvier and Schmidt-Lanterman incisures: an in vivo lanthanum tracer study

    J. Neurocytol.

    (1984)
  • T.J. Raub et al.

    Permeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglial cells

    Exp. Cell Res.

    (1992)
  • W. Risau

    Induction of blood-brain barrier endothelial cell differentiation

    Ann. NY Acad. Sci.

    (1991)
  • J.M. Rosenstein et al.

    Immunocytochemical expression of the endothelial barrier antigen (EBA) during brain angiogenesis

    Dev. Brain Res.

    (1992)
  • Y. Sato et al.

    Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-β 1-like molecule by plasmin during co-culture

    J. Cell Biol.

    (1989)
  • C. Schulze et al.

    Interendothelial junctions during blood-brain barrier development in the rat: morphological changes at the level of individual tight junctional contacts

    Dev. Brain Res.

    (1992)
  • M. Simionescu et al.

    Ultrastructure of the microvascular wall: functional correlations

  • Q.R. Smith et al.

    Cerebrovascular permeability coefficients to sodium potassium and chloride

    J. Neurochem.

    (1986)
  • N.H. Sternberger et al.

    Blood-brain barrier protein recognized by monoclonal antibody

  • J.-H. Tao-Cheng et al.

    Tight junctions of brain endothelium in vitro are enhanced by astroglia

    J. Neurosci.

    (1987)
  • A.W. Vorbrodt

    Glycoconjugates and anionic sites in the bloodbrain barrier

  • N.J. Abbott et al.

    Astrocyte-endothelial interaction: physiology and pathology

    Neuropathol. Appl. Neurobiol.

    (1992)
  • D.R. Anderson

    Ultrastructure of meningeal sheaths. Normal human and monkey optic nerves

    Arch. Ophthalmol.

    (1969)
  • D.R. Anderson et al.

    Ultrastructure of intraorbital portion of human and monkey optic nerve

    Arch. Ophthalmol.

    (1969)
  • A. Antonelli-Orlidge et al.

    An activated form of transforming growth factor is produced by cocultures of endothelial cells and pericytes

  • M.W.B. Bradbury

    The blood-brain barrier

    Exp. Physiol.

    (1993)
  • M.W. Brightman

    Ultrastructure of brain endothelium

  • M.W. Brightman et al.

    Junctions between intimately apposed cell membranes in the vertebrate brain

    J. Cell Biol.

    (1969)
  • M.W. Brightman et al.

    Tight junctions of brain endothelium and epithelium

  • R.D. Broadwell

    Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal

    Acta Neuropathol. (Berl.)

    (1989)
  • A.M. Butt et al.

    Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study

    J. Physiol.

    (1990)
  • P.A. Cancilla et al.

    Brain endothelial-astrocyte interactions

  • J.P. Cassella et al.

    Ontogeny of four blood-brain barrier markers: an immunocytochemical comparison of pial and cerebral cortical microvessels

    J. Anat.

    (1996)
  • J.P. Cassella et al.

    Rat pial microvasculature: the incomplete expression of a blood-brain barrier?

    Ann. Anat.

    (1996)
  • P. Claude et al.

    Fracture faces of zonulae occludentes from ‘tight’ and ‘leaky’ epithelia

    J. Cell Biol.

    (1973)
  • B.L. Coomber et al.

    Morphometric analysis of CNS microvascular endothelium

    Microvasc. Res.

    (1985)
  • C. Crone et al.

    Electrical resistance of brain microvascular endothelium

    Brain Res.

    (1982)
  • R. Dermietzel et al.

    Molecular anatomy of the bloodbrain barrier as defined by immunocytochemistry

    Intern. Rev. Cytol.

    (1991)
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