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

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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.

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Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, H-6726, Szeged, Hungary

    Mária A. Deli

  2. N-Gene Research Laboratories, Csillagvirág utca 8, H-1106, Budapest, Hungary

    Csongor S. Ábrahám

  3. Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Fukuoka, 814-0180, Japan

    Yasufumi Kataoka

  4. Department of Pharmacology 1, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Masami Niwa

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  1. Mária A. Deli
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  2. Csongor S. Ábrahám
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  3. Yasufumi Kataoka
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  4. Masami Niwa
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Correspondence to Mária A. Deli.

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Deli, M.A., Ábrahám, C.S., Kataoka, Y. et al. Permeability Studies on In Vitro Blood–Brain Barrier Models: Physiology, Pathology, and Pharmacology. Cell Mol Neurobiol 25, 59–127 (2005). https://doi.org/10.1007/s10571-004-1377-8

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