Glial influence on the blood brain barrier

Alvarez, Jorge Iván; Katayama, Takahiro; Prat, Alexandre

doi:10.1002/glia.22575

Cited by 434 publications

(361 citation statements)

References 215 publications

(275 reference statements)

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“…Interestingly, transendothelial electrical resistance (TEER) and permeability experiments showed that activation of the Hh pathway induced expression of junctional proteins and promoted a BBB phenotype. In addition, mice genetically engineered to lose the signal transducer Smo on ECs had a significant increase in BBB permeability that correlated with a decrease in junctional protein expression and disturbed BMs (Alvarez et al 2011a(Alvarez et al , 2013, supporting the concept that the Hh pathway has a significant influence on BBB function.…”

Section: Regulation Of the Bbb By Astrocytesmentioning

confidence: 63%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

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2,275

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Section: Regulation Of the Bbb By Astrocytesmentioning

confidence: 63%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

Self Cite

2,275

1,829

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“…However, there are probably many different BBB-inducing factors and cell-cell interactions, 25,26 not all of which have yet been fully characterized. 27 We therefore preferred to maintain the coculture feature that reliably reproduces the BBB phenotype 11 and therefore worked to adapt our original coculture model to use with large-pore-size inserts.…”

Section: Discussionmentioning

confidence: 99%

Adapting coculture in vitro models of the blood–brain barrier for use in cancer research: maintaining an appropriate endothelial monolayer for the assessment of transendothelial migration

Vandenhaute¹,

Drolez²,

Sevin³

et al. 2016

Laboratory Investigation

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Although brain metastases are the most common brain tumors in adults, there are few treatment options in this setting. To colonize the brain, circulating tumor cells must cross the blood-brain barrier (BBB), which is situated within specialized, restrictive microvascular endothelium. Understanding how cancer cells manage to transmigrate through the BBB might enable this process to be prevented. In vitro models are dedicated tools for characterizing the cellular and molecular mechanisms that underlie transendothelial migration process, as long as they accurately mimic the brain endothelium's in vivo characteristics. The objective of the present study was to adapt an existing in vitro model of the human BBB for use in studying cancer cell transmigration. The model is based on the coculture of endothelial cells (ECs, derived from cord blood hematopoietic stem cells) and brain pericytes. To allow the migration of cancer cells into the lower compartment, our model had to be transposed onto inserts with a larger pore size. However, we encountered a problem when culturing ECs on large (3-μm)-pore inserts: the cells crossed the membrane and formed a non-physiological second layer on the lower face of the insert. Using 3-μm-pore inserts (in a 12-well plate format), we report here on a method that enables the maintenance of a single monolayer of ECs on the insert's upper face only. Under these chosen conditions, the ECs exhibited typical BBB properties found in the original model (including restricted paracellular permeability and the expression of continuous tight junctions). This modified in vitro model of the human BBB enabled us to investigate the migratory potential of the MDA-MB-231 cell line (derived from highly metastatic human breast cancer cells). Last, the results obtained were compared with the rate of transmigration through endothelia with no BBB features.

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“…The role of astrocytes in the brain immunity has been documented mainly in pathological conditions (Alvarez et al, 2013;Jensen et al, 2013). In particular, astrocytes have been shown to sense the presence of pathogens and to control the entry of immune cells during neuroinflammation through the secretion of factors such as VEGF, Sonic Hedgehog, or retinoic acid (Alvarez et al, 2011;Argaw et al, 2012;Mizee et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Barrier properties of brain endothelium also depend on surrounding specialized cells, pericytes (Sá-Pereira et al, 2012) and astrocytes, the major glial cells in the brain, which project their endfeed around vessels and elaborate the so-called neurovascular unit (Abbott et al, 2006). Astrocytes have been shown to perform a range of vascular regulatory activities, maintaining BBB integrity (Abbott et al, 2006;Alvarez et al, 2013), coordinating blood flow (Petzold and Murthy, 2011), and regulating metabolite transfer to neurons (Bélanger et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Immune Quiescence of the Brain Is Set by Astroglial Connexin 43

et al. 2015

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In the normal brain, immune cell trafficking and immune responses are strictly controlled and limited. This unique homeostatic equilibrium, also called brain immune quiescence, is crucial to maintaining proper brain functions and is altered in various pathological processes, from chronic immunopathological disorders to cognitive and psychiatric impairments. To date, the precise nature of factors regulating the brain/immune system interrelationship is poorly understood. In the present study, we demonstrate that one of these regulating factors is Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the blood-brain barrier (BBB) interface. We show that, by setting the activated state of cerebral endothelium, astroglial Cx43 controls immune recruitment as well as antigen presentation mechanisms in the mouse brain. Consequently, in the absence of astroglial Cx43, recruited immune cells elaborate a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein of the brain. Altogether, our results demonstrate that Cx43 is a new astroglial factor promoting the immune quiescence of the brain.

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Glial influence on the blood brain barrier

Cited by 434 publications

References 215 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

Adapting coculture in vitro models of the blood–brain barrier for use in cancer research: maintaining an appropriate endothelial monolayer for the assessment of transendothelial migration

Immune Quiescence of the Brain Is Set by Astroglial Connexin 43

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