The characterization of arachnoid cell transport II: Paracellular transport and blood–cerebrospinal fluid barrier formation

Lam, Cornelius H.; Hansen, Eric A.; Janson, Christopher G.; Bryan, Alexander D.; Hubel, Allison

doi:10.1016/j.neuroscience.2012.06.065

Cited by 18 publications

(12 citation statements)

References 56 publications

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“…It has recently proved possible to culture arachnoid cells in vitro, which express claudin 1 and generate a TEER of ~160 Ω cm 2 with restriction of larger solute permeation (Lam et al , 2012Janson et al 2011 ). Characterization of the expression patterns of drug transporters and enzymes in arachnoid tissue and arachnoid barrier (AB) cells shows expression of both P-gp and breast cancer resistance protein (BCRP); an immortalized cell line of AB cells showed P-gp expression on the apical (dura-facing) membrane, and BCRP on both apical and basal (CSF-facing) membranes (Yasuda et al 2013 ).…”

Section: Arachnoid Epithelial Cellsmentioning

confidence: 99%

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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Section: Arachnoid Epithelial Cellsmentioning

confidence: 99%

In Vitro Models of CNS Barriers

Abbott

Dolman

Yusof

et al. 2013

AAPS Advances in the Pharmaceutical Sciences Series

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“…Herein, we tested the effect of two different TJ openers, EDTA and vandylacetylacetonate (VO(acac) 2 ). EDTA causes reversible TJ opening by depleting Ca 2+ and Mg 2+ that maintains the structure and conformation of TJ proteins5152; while, vanadium complexes can increase paracellular permeability through induction of oxidative stress, which was regarded as one of the major mechanism for the toxicity of these anti-diabetic agents10.…”

Section: Resultsmentioning

confidence: 99%

Exploring tight junction alteration using double fluorescent probe combination of lanthanide complex with gold nanoclusters

Wang

Yuan

et al. 2016

Sci Rep

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Tight junctions play a key role in restricting or regulating passage of liquids, ions and large solutes through various biological barriers by the paracellular route. Changes in paracellular permeation indicate alteration of the tight junction. However, it is very difficult to obtain the structural change information by measuring paracellular flux based on transepithelial electrical resistance or using fluorescein-labeled dextrans. Here we show that the BSA and GSH stabilized gold nanoclusters exhibit marginal cytotoxicity and pass through the MDCK monolayer exclusively through the paracellular pathway. We propose a double fluorescence probe strategy, the combination of a proven paracellular indicator (europium complex) with fluorescent gold nanoclusters. We calculate changes of structural parameters in tight junctions based on determination of the diffusion coefficients of the probes. Two different types of tight junction openers are used to validate our strategy. Results show that EDTA disrupts tight junction structures and induces large and smooth paracellular pore paths with an average radius of 17 nm, but vanadyl complexes induce paths with the radius of 6 nm. The work suggests that the double fluorescence probe strategy is a useful and convenient approach for in vitro investigation of tight junction structural alternations caused by pharmacological or pathological events.

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“…These data correlate with TEER results that indicated that lymphatic endothelium is semi‐permeable. The cells do not form a highly selective barrier as some other types of endothelial cells where tight junctions are present, such as arachnoid cells .…”

Section: Discussionmentioning

confidence: 99%