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Open Access 01-12-2015 | Review

Adenosine receptor signaling: a key to opening the blood–brain door

Authors: Margaret S. Bynoe, Christophe Viret, Angela Yan, Do-Geun Kim

Published in: Fluids and Barriers of the CNS | Issue 1/2015

Abstract

The aim of this review is to outline evidence that adenosine receptor (AR) activation can modulate blood–brain barrier (BBB) permeability and the implications for disease states and drug delivery. Barriers of the central nervous system (CNS) constitute a protective and regulatory interface between the CNS and the rest of the organism. Such barriers allow for the maintenance of the homeostasis of the CNS milieu. Among them, the BBB is a highly efficient permeability barrier that separates the brain micro-environment from the circulating blood. It is made up of tight junction-connected endothelial cells with specialized transporters to selectively control the passage of nutrients required for neural homeostasis and function, while preventing the entry of neurotoxic factors. The identification of cellular and molecular mechanisms involved in the development and function of CNS barriers is required for a better understanding of CNS homeostasis in both physiological and pathological settings. It has long been recognized that the endogenous purine nucleoside adenosine is a potent modulator of a large number of neurological functions. More recently, experimental studies conducted with human/mouse brain primary endothelial cells as well as with mouse models, indicate that adenosine markedly regulates BBB permeability. Extracellular adenosine, which is efficiently generated through the catabolism of ATP via the CD39/CD73 ecto-nucleotidase axis, promotes BBB permeability by signaling through A₁ and A_2A ARs expressed on BBB cells. In line with this hypothesis, induction of AR signaling by selective agonists efficiently augments BBB permeability in a transient manner and promotes the entry of macromolecules into the CNS. Conversely, antagonism of AR signaling blocks the entry of inflammatory cells and soluble factors into the brain. Thus, AR modulation of the BBB appears as a system susceptible to tighten as well as to permeabilize the BBB. Collectively, these findings point to AR manipulation as a pertinent avenue of research for novel strategies aiming at efficiently delivering therapeutic drugs/cells into the CNS, or at restricting the entry of inflammatory immune cells into the brain in some diseases such as multiple sclerosis.

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Title: Adenosine receptor signaling: a key to opening the blood–brain door
Authors: Margaret S. Bynoe
Christophe Viret
Angela Yan
Do-Geun Kim
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Fluids and Barriers of the CNS / Issue 1/2015
Electronic ISSN: 2045-8118
DOI: https://doi.org/10.1186/s12987-015-0017-7

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Adenosine receptor signaling: a key to opening the blood–brain door

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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