The Cerebral Microvessels in Culture, an Update

Joó, Ferenc

doi:10.1111/j.1471-4159.1992.tb09272.x

Cited by 132 publications

(17 citation statements)

References 153 publications

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“…The cell culture insert/filter setup made it possible to use brain endothelial cells for coculture and permeability studies in vitro (Joó, 1992). The first studies used monocultures (Abbott et al, 1992;Bowman et al, 1981Bowman et al, , 1983Panula et al, 1978;Rutten et al, 1987; Table I), but it turned out very soon, that cultivation of brain endothelial cells alone leads to loss of phenotype, for example, a specific enzyme, γ-glutamyl transpeptidase, that can be restored by coculture with glial cells (DeBault and Cancilla, 1980).…”

Section: -69 Bmentioning

confidence: 98%

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

et al. 2005

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(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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Section: -69 Bmentioning

confidence: 98%

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

et al. 2005

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“…The fi rst successful isolation of cerebral microvessels (Siakotos and Rouser 1969 ;Joó and Karnushina 1973 ) prepared the way for development of in vitro models of the blood-brain barrier (BBB), which have contributed to current understanding of its physiology, pharmacology and pathophysiology (reviewed in Joó 1992 ). Methods have also been developed for in vitro models of the choroid plexus and of the arachnoid epithelium (blood-CSF barrier, BCSFB).…”

Section: Background and Early Historymentioning

confidence: 98%

In Vitro Models of CNS Barriers

Abbott

Dolman

Yusof

et al. 2013

AAPS Advances in the Pharmaceutical Sciences Series

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This chapter reviews the history and modern applications of isolated preparations of the three main CNS barrier layers and cell culture preparations derived from them. In vitro models give valuable mechanistic information but also provide useful assay systems for drug discovery and delivery programmes. However, it is important to take into account practical issues including species differences and the degree to which the differentiated state of the in vivo barrier is retained. The range of models available is reviewed, with a critical evaluation of their strengths and weaknesses, and guidance in selecting and optimizing a suitable model for particular applications. New understanding of the unstirred water layers and paracellular leak pathway in in vitro preparations gives greater insights into the "intrinsic permeability" of the membrane, and a variety of techniques permit characterization of the transport systems and enzymes contributing to barrier function. Increasingly, aspects of CNS pathology are being modelled in cell culture, aiding the optimization of drug delivery regimes in pathological conditions. Chapter 6In Vitro Models of CNS Barriers IntroductionFrom the earliest demonstration of restricted exchange between the blood and the brain (Ehrlich 1885 ) leading to the modern understanding of the blood-CNS barriers, animal experiments and clinical observations have provided valuable information about the physiology and pathology of the barrier layers. However, obtaining mechanistic information from such studies at the cellular and molecular level is complex and time-consuming, and it is often diffi cult to obtain suffi cient spatial and temporal resolution. The situation was dramatically improved by the introduction of in vitro methods (reviewed in Joó 1992 ). Background and Early HistoryThe fi rst successful isolation of cerebral microvessels (Siakotos and Rouser 1969 ;Joó and Karnushina 1973 ) prepared the way for development of in vitro models of the blood-brain barrier (BBB), which have contributed to current understanding of its physiology, pharmacology and pathophysiology (reviewed in Joó 1992 ). Methods have also been developed for in vitro models of the choroid plexus and of the arachnoid epithelium (blood-CSF barrier, BCSFB). However, this proliferation of in vitro models and techniques causes problems for attempts at comparison between models and transferability of results obtained with different models, and makes it hard for scientists entering the fi eld to select an optimal model for their particular interests. This chapter gives an overview of the current status of the most widely used in vitro CNS barrier models, with an update on an earlier review (Reichel et al. 2003 ), and offers guidance in model selection for specifi c applications, including permeability assay for drugs and "new chemical entities" (NCEs). Isolated brain microvessels were the fi rst model system for studying the BBB in vitro, offering new opportunities to investigate physiological and pathological processes at...

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“…Various approaches have been made to create a cell culture model of the blood-brain barrier (for review, see Joó, 1992;Laterra and Goldstein, 1993). Most of them are based on primary culture of BCECs, although immortalized cell lines of BCECs have also been used (Roux et al, 1994;Muruganandam et al, 1997).…”

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confidence: 99%

Basement Membrane Proteins Influence Brain Capillary Endothelial Barrier Function In Vitro

Tilling

Korte

Hoheisel

et al. 1998

Journal of Neurochemistry

167

109

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Abstract:The influence of basement membrane proteins on cellular barrier properties of primary cultures of porcine brain capillary endothelial cells grown on permeable filter inserts has been investigated. Measurements of transcellular electrical resistance (TEA) by impedance spectroscopy were performed with cells cultured on type IV collagen, fibronectin, laminin, and one-to-one mixtures of these proteins. Moreover, a one-to-one combination of type IV collagen and SPARC (secreted protein acidic and rich in cysteine) has been studied. Rat tail collagen has been used as a reference substratum. If TERs of cells from a given preparation were low (-~350Q x cm 2) on the reference substratum, type IV collagen, fibronectin, and laminin as well as one-to-one combinations of these proteins elevated transcellular resistances significantly (2.3-to 2.9-fold) compared with rat tail collagen. TER of cells exhibiting a high reference level (~-~1 000~l x cm2) could, by contrast, be increased only 1.1-to 1.2-fold. The type IV collagen/SPARC mixture did not elevate TER. Our findings suggest that type IV collagen, fibronectin, and laminin are involved in tight junction formation between cerebral capillary endothelial cells. The differential effects observed for individual preparations probably reflect more or less dedifferentiated states of the endothelium, in which basement membrane proteins can influence cellular differentiation more or less strongly. However, our results indicate that type IV collagen, fibronectin, and laminin enhance the reliability and suitability of primary microvascular endothelial cell cultures as an in vitro model of the blood-brain barrier. Key Words: Bloodbrain barrier-Primary cell culture-Transcellular electrical resistance-Basement membrane proteins-Extracellular matrix.

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The Cerebral Microvessels in Culture, an Update

Cited by 132 publications

References 153 publications

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

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

In Vitro Models of CNS Barriers

Basement Membrane Proteins Influence Brain Capillary Endothelial Barrier Function In Vitro

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