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Cellular and Molecular Neurobiology

, Volume 25, Issue 1, pp 59–127 | Cite as

Permeability Studies on In Vitro Blood–Brain Barrier Models: Physiology, Pathology, and Pharmacology

  • Mária A. Deli
  • Csongor S. Ábrahám
  • Yasufumi Kataoka
  • Masami Niwa
Article

Summary

1. The specifically regulated restrictive permeability barrier to cells and molecules is the most important feature of the blood–brain barrier (BBB). The aim of this review was to summarize permeability data obtained on in vitro BBB models by measurement of transendothelial electrical resistance and by calculation of permeability coefficients for paracellular or transendothelial tracers.

2. Results from primary cultures of cerebral microvascular endothelial cells or immortalized cell lines from bovine, human, porcine, and rodent origin are presented. Effects of coculture with astroglia, neurons, mesenchymal cells, blood cells, and conditioned media, as well as physiological influence of serum components, hormones, growth factors, lipids, and lipoproteins on the barrier function are discussed.

3. BBB permeability results gained on in vitro models of pathological conditions including hypoxia and reoxygenation, neurodegenerative diseases, or bacterial and viral infections have been reviewed. Effects of cytokines, vasoactive mediators, and other pathogenic factors on barrier integrity are also detailed.

4. Pharmacological treatments modulating intracellular cyclic nucleotide or calcium levels, and activity of protein kinases, protein tyrosine phosphatases, phospholipases, cyclooxygenases, or lipoxygenases able to change BBB integrity are outlined. Barrier regulation by drugs involved in the metabolism of nitric oxide and reactive oxygen species, as well as influence of miscellaneous treatments are also listed and evaluated.

5. Though recent advances resulted in development of improved in vitro BBB model systems to investigate disease modeling, drug screening, and testing vectors targeting the brain, there is a need for checking validity of permeability models and cautious interpretation of data.

Key words

blood–brain barrier cerebral endothelial cells coculture in vitro model permeability transendothelial electrical resistance. 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Mária A. Deli
    • 1
  • Csongor S. Ábrahám
    • 2
  • Yasufumi Kataoka
    • 3
  • Masami Niwa
    • 4
  1. 1.Laboratory of Molecular Neurobiology, Institute of BiophysicsBiological Research Centre of the Hungarian Academy of SciencesSzegedHungary
  2. 2.N-Gene Research LaboratoriesBudapestHungary
  3. 3.Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical SciencesFukuoka UniversityFukuokaJapan
  4. 4.Department of Pharmacology 1Nagasaki University School of MedicineNagasakiJapan

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