Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model

Arthur, Fred E.; Shivers, Richard R.; Bowman, Phillip D.

doi:10.1016/0165-3806(87)90075-7

Cited by 326 publications

(127 citation statements)

References 13 publications

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“…tightness), and protein expression [3,6,12,58,81]. However, it remains unclear whether or not promotion of the endothelial barrier function by astrocytes requires a direct contact between astrocytes and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

et al. 2007

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The blood-brain barrier (BBB) is a structural and functional barrier that regulates the passage of molecules into and out of the brain to maintain the neural microenvironment. We have previously developed the in vitro BBB model with human brain microvascular endothelial cells (HBMEC). However, in vivo HBMEC are shown to interact with astrocytes and also exposed to shear stress through blood flow. In an attempt to develop the BBB model to mimic the in vivo condition we constructed the flow-based in vitro BBB model using HBMEC and human fetal astrocytes (HFA). We also examined the effect of astrocyte conditioned medium (ACM) in lieu of HFA to study the role of secreted factor(s) on the BBB properties. The tightness of HBMEC monolayer was assessed by the permeability of dextran and propidium iodide as well as by measuring the transendothelial electrical resistance (TEER). We showed that the HBMEC permeability was reduced and TEER was increased by non-contact, co-cultivation with HFA and ACM. The exposure of HBMEC to shear stress also exhibited decreased permeability. Moreover, HFA/ACM and shear flow exhibited additive effect of decreasing the permeability of HBMEC monolayer. In addition, we showed that the HBMEC expression of ZO-1 (tight junction protein) was increased by co-cultivation with ACM and in response to shear stress. These findings suggest that the non-contact co-cultivation with HFA helps maintain the barrier properties of HBMEC by secreting factor(s) into the medium. Our in vitro flow model system with the cells of human origin should be useful for studying the interactions between endothelial cells, glial cells, and secreted factor(s) as well as the role of shear stress in the barrier property of HBMEC.

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Section: Discussionmentioning

confidence: 99%

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

et al. 2007

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“…Vascular endothelial growth factor, the powerful permeability factor that is produced in the retina by neurons and glia (33,34), has been found increased in the diabetic rat retina (34), and the increase was prevented by aldose reductase inhibition (35). Dysfunctional glial cells could further contribute to the increased permeability of retinal vessels if they alter their contribution to the formation of tight junctions (36,37). Material attributable to GFAP-positive Mü ller cells is present in the former lumen of ghost vessels in human diabetic retinopathy, raising the possibility of a glial role in vascular occlusion (38,39).…”

Section: Discussionmentioning

confidence: 99%

A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat

Asnaghi

Gerhardinger²,

Hoehn³

et al. 2003

Diabetes

252

196

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We tested the hypothesis that the apoptosis of inner retina neurons and increased expression of glial fibrillary acidic protein (GFAP) observed in the rat after a short duration of diabetes are mediated by polyol pathway activity. Rats with 10 weeks of streptozotocininduced diabetes and GHb levels of 16 ؎ 2% (mean ؎ SD) showed increased retinal levels of sorbitol and fructose, attenuation of GFAP immunostaining in astrocytes, appearance of prominent GFAP expression in Mü ller glial cells, and a fourfold increase in the number of apoptotic neurons when compared with nondiabetic rats. The cells undergoing apoptosis were immunoreactive for aldose reductase. Sorbinil, an inhibitor of aldose reductase, prevented all abnormalities. Intensive insulin treatment also prevented most abnormalities, despite reducing GHb only to 12 ؎ 1%. Diabetic mice, known to have much lower aldose reductase activity in other tissues when compared with rats, did not accumulate sorbitol and fructose in the retina and were protected from neuronal apoptosis and GFAP changes in the presence of GHb levels of 14 ؎ 2%. This work documents discrete cellular consequences of polyol pathway activity in the retina, and it suggests that activation of the pathway and "retinal neuropathy" require severe hyperglycemia and/or high activity of aldose reductase. These findings have implications for how to evaluate the role of the polyol pathway in diabetic retinopathy.

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“…In the BBB, G G T expression must respond to local inducers, since the enzyme is not ubiquitous in all capillary beds. Astrocytes are believed to be responsible for this induction and for the development of the BBB in general (Arthur et al, 1987;De Bault and Cancilla, 1980;Janzer and Raff, 1987). Coculturing systems of astrocytes and noncerebral endothelial cells partially mimic BBB, since G G T expression is triggered in such systems (Gebhart and Goldstein, 1988).…”

Section: Discussionmentioning

confidence: 99%

Pericytes of the brain microvasculature express γ‐glutamyl transpeptidase

Frey

Meckelein

Weiler-Güttler

et al. 1991

European Journal of Biochemistry

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The expression of y-glutamyl transpeptidase (GGT) is a specific property of the brain capillary endothelium that constitutes the blood-brain barrier. We report here the detection of GGT, not only in endothelial cells, but also in pericytes, demonstrating that a brain capillary-specific pericyte population exists. We raised antibodies to GGT using a porcine brain microvessel GGT -protein-A (staphylococcal protein A) fusion protein as antigen which was expressed in Escherichia coli. The immunohistochemical analysis of the subcapillary distribution of GGT in porcine brain cortex and cerebellum sections by both light and electron microscopy revealed the expression of GGT in the capillary-adjacent pericytes in addition to the GGT-positive endothelial layer. We confirmed these data for cultured porcine brain microvascular endothelial cells and pericytes. GGT immunofluorescence could be detected in both cell types in culture. Endothelial cells exhibited a weak staining, whereas pericytes were strongly positive for GGT. Due to the high phagocytotic activity of pericytes and their location on the abluminal surface of the microvessels, we propose a possible protective or detoxifying function of GGT in cerebrovascular pericytes.

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Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model

Cited by 326 publications

References 13 publications

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat

Pericytes of the brain microvasculature express γ‐glutamyl transpeptidase

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