Differential permeability of cerebral capillary and choroid plexus to lanthanum ion

Bouldin, Thomas W.; Krigman, Martin R.

doi:10.1016/0006-8993(75)90053-0

Cited by 100 publications

(36 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus the similar K in values shown in Table 1 for the movement of [ 3 H]-D4T into the cerebellum and CSF con®rm that the BBB and the blood-CSF barrier have di ering permeability characteristics (Bouldin & Krigman, 1975). It has been suggested that the brain endothelium contains a low number of neutral or weakly charged, but highly permeable, hydrophilic pores (Crone, 1984).…”

Section: Discussionsupporting

confidence: 52%

“…The main function of the choroid plexus is to actively secrete CSF and a variety of proteins, while that of the BBB is to maintain solute gradients. In turn, both the cellular and paracellular permeability characteristics of the two barriers are quite di erent (Welch & Sadler, 1966;Bouldin & Krigman, 1975). Consequently the presence of a substance in the CSF does not necessarily re¯ect BBB permeability, but does relate to blood-CSF barrier permeability.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Thomas

Segal

1998

British J Pharmacology

View full text Add to dashboard Cite

1 The brain is a site of infection, viral replication and sanctuary for HIV-1. The treatment of HIV-1 infection therefore requires that an e ective agent be delivered to the brain. 2',3'-Didehydro-3'-deoxythymidine (D4T) is a nucleoside analogue which has been shown to have bene®cial clinical e ects in the treatment of HIV infection. However, although D4T has been detected in human CSF, the ability of this drug to cross both the blood-brain and blood-cerebrospinal¯uid (CSF) barriers and gain entrance into the brain tissue is not known. 2 This study examined the CNS entry of D4T by means of the bilateral vascular brain perfusion technique in the anaesthetized guinea-pig. 3 The results indicated that [ 3 H]-D4T had a limited ability to cross the blood-brain barrier (BBB), which was not signi®cantly greater than D-[ 14 C]-mannitol (a slowly penetrating marker molecule). Although D4T was found to cross the blood-CSF barrier, the presence of D4T in the CSF did not re¯ect levels of the drug in the brain tissue. 4 These results can be related to the measured low lipophilicity of D4T, the higher paracellular permeability characteristics of the choroid plexus (blood-CSF barrier) compared to the BBB, and the sink action nature of the CSF to the brain tissue. 5 In conclusion, these animal studies suggest that D4T may only penetrate the brain tissue to a limited extent and consideration should be given to these ®ndings in the clinical situation.

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Thomas

Segal

1998

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…The lanthanum ion -the smallest possible opaque marker in electron microscopy -is commonly considered an extracellular tracer that does not normally penetrate the BBB or cross the intact endothelium (Bouldin and Krigman, 1975;Brightman and Reese 1969;Hirano et al 1994). However, there have been descriptions of diffuse deposits of lanthanum in ECs, and there is some disagreement in the literature regarding the interpretation of such cytoplasmic accumulation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Focused Ultrasound Applied With an Ultrasound Contrast Agent on the Tight Junctional Integrity of the Brain Microvascular Endothelium

Sheikov

McDannold

Sharma

et al. 2008

Ultrasound in Medicine & Biology

415

358

View full text Add to dashboard Cite

Previous studies have investigated a potential method for targeted drug delivery in the central nervous system that uses focused ultrasound bursts combined with an ultrasound contrast agent to temporarily disrupt the blood-brain barrier (BBB). The purpose of this work was to investigate the integrity of the tight junctions (TJs) in rat brain microvessels after this BBB disruption. 1.5-MHz ultrasound bursts in combination with a gas contrast agent (Optison) was applied at two locations in the brain in 25 rats to induce BBB disruption. Using immunoelectron microscopy, the distributions of the TJspecific transmembrane proteins occludin, claudin-1, claudin-5, and of submembranous ZO-1 were examined at 1, 2, 4, 6 and 24 h after sonication. A quantitative evaluation of the protein expression was made by counting the number of immunosignals per micrometer in the junctional clefts. BBB disruption at the sonicated locations was confirmed by the leakage of intravenously administered horseradish peroxidase (HRP, m.w. 40,000 Da) and lanthanum chloride (La 3+ , m.w. ~ 139 Da). Leakage of these agents was observed at 1 and 2 h and in a few vessels at 4 h after ultrasound application. These changes were paralleled by the apparent disintegration of the TJ complexes, as evidenced by the redistribution and loss of the immunosignals for occludin, claudin-5 and ZO-1. Claudin-1 seemed less involved. At 6 and 24 h after sonication, no HRP or lanthanum leakage was observed, and the barrier function of the TJs, as indicated by the localization and density of immunosignals, appeared to be completely restored. This study provides the first direct evidence that ultrasound bursts combined with a gas contrast agent cause disassembling of the TJ molecular structure, leading to loss of the junctional barrier functions in brain microvessels. The BBB disruption appears to last up to 4 h after sonication and permits the paracellular passage of agents with molecular weights up to at least 40 kDa. These promising features can be exploited in the future development of this method that could enable the delivery of drugs, antibodies or genes to targeted locations in the brain.

show abstract

“…Using a VO system with a stable continuous subcultivatable porcine CPE cell line, Schroten et al ( 2012 ) reported TEER >600 Ω cm 2 . In general the values up to ~600 Ω cm 2 fi t better with evidence for leakier tight junctions in CPE than BBB (Bouldin and Krigman 1975 ), but it is clear that more "side-by-side" comparisons of VO and IS systems using a particular in vitro model would be helpful to clarify the situation. .…”

Section: Impedance Spectroscopy Systemsmentioning

confidence: 98%

In Vitro Models of CNS Barriers

Abbott

Dolman

Yusof

et al. 2013

AAPS Advances in the Pharmaceutical Sciences Series

View full text Add to dashboard Cite

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...

show abstract

Differential permeability of cerebral capillary and choroid plexus to lanthanum ion

Cited by 100 publications

References 10 publications

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Effect of Focused Ultrasound Applied With an Ultrasound Contrast Agent on the Tight Junctional Integrity of the Brain Microvascular Endothelium

In Vitro Models of CNS Barriers

Contact Info

Product

Resources

About