Differentiation of Brain Endothelial Cells in Cell Culture

Rubin, Lee L.; Barbu, K; Bard, Frédéric; Cannon, Catherine; Hall, Don; Horner, Heidi C.; Janatpour, Mary J.; Liaw, Chen; Manning, Kizzie; Morales, José María García Ruiz de; Porter, Seth; Tanner, L I; Tomaselli, Kevin J.; Yednock, Ted

doi:10.1111/j.1749-6632.1991.tb15631.x

Cited by 66 publications

(39 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immediately ex vivo brain microvascular ECs lose their transendothelial electrical resistance (TEER) (Rubin et al, 1991) and become permeable to soluble tracers (Prat et al, 2001). Strong TEER and better barrier properties can be reinduced when cells are grown in the presence of ACM (Arthur et al, 1987;Neuhaus et al, 1991;Abbott, 2002).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

View full text Add to dashboard Cite

The blood-brain barrier (BBB) restricts molecular and cellular trafficking between the blood and the CNS. Although astrocytes are known to control BBB permeability, the molecular determinants of this effect remain unknown. We show that angiotensinogen (AGT) produced and secreted by astrocytes is cleaved into angiotensin II (AngII) and acts on type 1 angiotensin receptors (AT 1 ) expressed by BBB endothelial cells (ECs). Activation of AT 1 restricts the passage of molecular tracers across human BBB-derived ECs through threonine-phosphorylation of the tight junction protein occludin and its mobilization to lipid raft membrane microdomains. We also show that AGT knock-out animals have disorganized occludin strands at the level of the BBB and a diffuse accumulation of the endogenous serum protein plasminogen in the CNS, compared with wild-type animals. Finally, we demonstrate a reduction in the number of AGT-immunopositive perivascular astrocytes in multiple sclerosis (MS) lesions, which correlates with a reduced expression of occludin similarly seen in the CNS of AGT knock-out animals. Such a reduction in astrocyte-expressed AGT and AngII is dependent, in vitro, on the proinflammatory cytokines tumor necrosis factor-␣ and interferon-␥. Our study defines a novel physiological role for AngII in the CNS and suggests that inflammation-induced downregulation of AngII production by astrocytes is involved in BBB dysfunction in MS lesions.

show abstract

Section: Discussionmentioning

confidence: 99%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

View full text Add to dashboard Cite

show abstract

“…It has also been studied indirectly using macromolecules such as dyes bound to proteins or HRP in permeability studies, again both in vivo and in vitro. In addition, measurement of transendothelial resistance in vivo (BUTT et al 1990) and in vitro (RUBIN et al 1991) has been used as an indirect measure of the diffusion restraint that is fundamental to all barrier mechanisms. In many studies HRP has been injected i.v.…”

Section: Formation Of the Fundamental Blood-brain And Blood-csf Bamentioning

confidence: 99%

Ontogenetic Development of Brain Barrier Mechanisms

Saunders¹

1992

Physiology and Pharmacology of the Blood-Brain Barrier

View full text Add to dashboard Cite

“…Studies have focused largely on brain endothelial cell and astrocyte interactions whose end-feet cover more than 90% of the cerebrovascular surface. In culture, endothelial cells lose their BBB characteristics (Rubin et al, 1991), but these are restored when co-cultured with cells of astroglial origin, incubated with astroglial membrane fractions or astrocyte/glioma-conditioned medium (Abbott et al, 1992;Hurst and Fritz, 1996;Reinhardt and Gloor, 1997;Sobue et al, 1999;Prat et al, 2001). It seems clear that, in culture at least, astroglia play a role in inducing BBB properties.…”

Section: Introductionmentioning

confidence: 96%

Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood‐brain barrier in the apparent absence of direct astrocytic contact

Willis

Nolan

Reith

et al. 2003

Glia

114

113

View full text Add to dashboard Cite

Blood-brain barrier (BBB) breakdown is a feature of cerebral ischaemia, multiple sclerosis, and other neurodegenerative diseases, yet the relationship between astrocytes and the BBB integrity remains unclear. We present a simple in vivo model in which primary astrocyte loss is followed by microvascular damage, using the metabolic toxin 3-chloropropanediol (S-alpha-chlorohydrin). This model is uncomplicated by trauma, ischaemia, or primary immune involvement, permitting the study of the role of astrocytes in vascular endothelium integrity, maintenance of the BBB, and neuronal function. Male Fisher F344 rats given 3-chloropropanediol show astrocytic damage and death at 4-24 h in symmetrical brainstem and midbrain nuclear lesions, while neurons show morphological changes at 24-48 h. Fluorescent 10 kDa dextran tracers show the BBB leaking from 24 h, progressing to petechial haemorrhage after 48-72 h, with apparent repair after 6 days. BBB breakdown, but not the earlier astrocytic death, is accompanied by a delayed increase in blood flow in the inferior colliculus. An ED1 inflammatory response develops well after astrocyte loss, suggesting that inflammation may not be a factor in starting BBB breakdown. This model demonstrates that the BBB can self-repair despite the apparent absence of direct astrocytic-endothelial contact. The temporal separation of pathological events allows pharmacological intervention, and the mild reversible ataxia permits long-term survival studies of repair mechanisms.

show abstract

Differentiation of Brain Endothelial Cells in Cell Culture

Cited by 66 publications

References 15 publications

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Ontogenetic Development of Brain Barrier Mechanisms

Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood‐brain barrier in the apparent absence of direct astrocytic contact

Contact Info

Product

Resources

About