title: Adenosine A2A receptors modulate acute injury and neuroinflammation in brain ischemia.
abstract: The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A(2A) receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A(2A) 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. A(2A) 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 A(2A) receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A(2A) 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 A(2A) receptor agonists a wide therapeutic time-window of hours and even days after stroke.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Felicita
authors.initials: F
authors.lastname: Pedata
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pugliese
authors.affiliation: Department of Health Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Coppi
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dettori
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Maraula
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Cellai
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Melani
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
chemical_list: D016207:Cytokines; D043705:Receptor, Adenosine A2A