In vitro models for the blood–brain barrier

Garberg, Per; Ball, Marguerite; Borg, Natalia; Cecchelli, Roméo; Fénart, Laurence; Hurst, Roger D.; Lindmark, Tuulikki; Mabondzo, Aloı̈se; Nilsson, Jeanette; Raub, Thomas J.; Stanimirovic, Danica; Terasaki, Tetsuya; Öberg, Johanna; Österberg, Thomas

doi:10.1016/j.tiv.2004.06.011

Cited by 365 publications

(316 citation statements)

References 19 publications

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“…It binds to FGF receptor 1 (FGFR1) on endothelial cells, exhibits a wide range of angiotrophic effects, and activates signaling pathways involved in regulating endothelial cell survival (Garberg, 1998;Sobue et al, 1999). FGF-2 has also been found to decrease the permeability of the BBB in vitro (El Hafny et al, 1996), which is consistent with the finding that mutant mice lacking FGF-2 show decreased levels of the tight junction proteins occludin and ZO-1 and defects in BBB function (Reuss et al, 2003).…”

Section: Introductionsupporting

confidence: 62%

“…Here, we have taken advantage of FGF-2 as a key molecule in modulating the BBB, promoting angiogenesis and regulating endothelial cell survival (Garberg, 1998;Sobue et al, 1999). Several studies have implicated astrocytes or astrocytic factors in the development and maintenance of BBB properties in endothelial cells of the brain (Bauer and Bauer, 2000;Garberg, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have implicated astrocytes or astrocytic factors in the development and maintenance of BBB properties in endothelial cells of the brain (Bauer and Bauer, 2000;Garberg, 1998). Among the known astrocyte-derived growth factors, only FGF-2 mimics the signaling actions of astrocytes to the BBB Sobue et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…FGF-2 is produced primarily by astrocytes in close proximity to endothelial cells of the BBB (Sobue et al, 1999) and mimics the signaling actions of astrocytes to the BBB (Garberg, 1998. It binds to FGF receptor 1 (FGFR1) on endothelial cells, exhibits a wide range of angiotrophic effects, and activates signaling pathways involved in regulating endothelial cell survival (Garberg, 1998;Sobue et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A NewIn VitroModel of the Blood–Brain Barrier

Bendfeldt¹,

Radojević²,

Kapfhammer³

et al. 2007

J. Neurosci.

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This study was performed to examine the maintenance of blood vessels in vitro in cortical organotypic slice cultures of mice with special emphasis on basic fibroblast growth factor (FGF-2), which is known to promote angiogenesis and to preserve the integrity of the blood-brain barrier. Slices of neonatal day 3 or 4 mouse brain were maintained for 3, 7, or 10 d in vitro (DIV) under standard culture conditions or in the presence of FGF-2. Immunohistochemistry for factor VIII-related antigen or laminin revealed a relative low number of blood vessels under standard conditions. In contrast, moderate FGF-2 concentrations increased the number of vessels: with 0.5 ng/ml FGF-2 it was 1.4-fold higher after DIV 3 or 1.5-fold after DIV 7 compared with controls; with 5 ng/ml it was almost doubled in both cases. With an excess of 50 ng/ml, FGF-2 vessels were reduced after DIV 3 or similar to controls after DIV 7. FGF receptor 1 was preferentially found on endothelial cells; its immunolabeling was reduced in the presence of the ligand. Cell death detected by an ethidium bromide analog or the apoptosis marker caspase-3 was barely detectable during the 10 d culture period. Immunolabeling of the tight junction proteins ZO-1 (zonula occludens protein 1), occludin, claudin-5, and claudin-3 revealed evidence for structural integrity of the bloodbrain barrier in the presence of moderate FGF-2 concentrations. In conclusion, FGF-2 maintains blood vessels in vitro and preserves the composition of the tight junction. Hence, we propose FGF-2-treated organotypic cortical slices as a new tool for mechanistic studies of the blood-brain barrier.

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Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A NewIn VitroModel of the Blood–Brain Barrier

Bendfeldt¹,

Radojević²,

Kapfhammer³

et al. 2007

J. Neurosci.

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“…The cell specimen was viewed with fluorescence microscope. Establishment of the in Vitro BBB Model 16) ECV304 and astrocytes were cocultured in a "contact through feet" model. In a 12-well cell culture insert with 1 mm-diameter microporous polyethylene terephthalate (PET) membrane (Falcon, 1 mm pore size, 10.5 mm diameter, 0.9 cm 2 surface area), astrocytes were transferred at second passage on the bottom side at a density of 1.0ϫ10 6 cells/ml by placing the insert upside down.…”

Section: Methodsmentioning

confidence: 99%

Improving Efficiency of Adriamycin Crossing Blood Brain Barrier by Combination of Thermosensitive Liposomes and Hyperthermia

Gong

Wang

Liu

et al. 2011

Biological & Pharmaceutical Bulletin

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Overview of Experimental Models of the Blood‐Brain Barrier in CNS Drug Discovery

Palmer¹,

Alavijeh

2013

CP Pharmacology

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The blood-brain barrier (BBB) is a physical and metabolic entity that isolates the brain from the systemic circulation. The barrier consists of tight junctions between endothelial cells that contain egress transporters and catabolic enzymes. To cross the BBB, a drug must possess the appropriate physicochemical properties to achieve a sufficient time-concentration profile in brain interstitial fluid (ISF). In this overview, we review techniques to measure BBB permeation, which is evidenced by the free concentration of compound in brain ISF over time. We consider a number of measurement techniques, including in vivo microdialysis and brain receptor occupancy following perfusion. Consideration is also given to the endothelial and nonendothelial cell systems used to assess both the BBB permeation of a test compound and its interactions with egress transporters, and computer models employed for predicting passive permeation and the probability of interactions with BBB transporters.

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In vitro models for the blood–brain barrier

Cited by 365 publications

References 19 publications

Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A NewIn VitroModel of the Blood–Brain Barrier

Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A NewIn VitroModel of the Blood–Brain Barrier

Improving Efficiency of Adriamycin Crossing Blood Brain Barrier by Combination of Thermosensitive Liposomes and Hyperthermia

Overview of Experimental Models of the Blood‐Brain Barrier in CNS Drug Discovery

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