Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive ta...

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Main Authors: Felicita Pedata, Anna Maria Pugliese, Elisabetta Coppi, Ilaria Dettori, Giovanna Maraula, Lucrezia Cellai, Alessia Melani
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/805198
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author Felicita Pedata
Anna Maria Pugliese
Elisabetta Coppi
Ilaria Dettori
Giovanna Maraula
Lucrezia Cellai
Alessia Melani
author_facet Felicita Pedata
Anna Maria Pugliese
Elisabetta Coppi
Ilaria Dettori
Giovanna Maraula
Lucrezia Cellai
Alessia Melani
author_sort Felicita Pedata
collection DOAJ
description The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.
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publishDate 2014-01-01
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series Mediators of Inflammation
spelling doaj-art-0094835e37e24903912c47cf9b36b24d2025-02-03T05:48:09ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/805198805198Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain IschemiaFelicita Pedata0Anna Maria Pugliese1Elisabetta Coppi2Ilaria Dettori3Giovanna Maraula4Lucrezia Cellai5Alessia Melani6Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Health Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyThe extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.http://dx.doi.org/10.1155/2014/805198
spellingShingle Felicita Pedata
Anna Maria Pugliese
Elisabetta Coppi
Ilaria Dettori
Giovanna Maraula
Lucrezia Cellai
Alessia Melani
Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
Mediators of Inflammation
title Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
title_full Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
title_fullStr Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
title_full_unstemmed Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
title_short Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia
title_sort adenosine a2a receptors modulate acute injury and neuroinflammation in brain ischemia
url http://dx.doi.org/10.1155/2014/805198
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