title: Adenosine receptors in cerebral ischemia.
abstract: Ischemic stroke is a complex pathology characterized by a sequence of events that evolve over time and space. It is the second leading cause of death and the main cause of adult long-term disability in developed countries. At the moment, there is no promising pharmacotherapy for acute ischemic stroke. Adenosine receptors (A1, A2A, A2B, A3) are important targets for therapeutic implementation in the treatment of stroke because extracellular adenosine concentrations increase dramatically soon after ischemia. Adenosine receptors located both on central nervous system cells and on immune blood cells exert important roles during ischemia. The neuroprotective role of adenosine through A1 receptor subtype during ischemia is accepted, but the use of selective A1 agonists is hampered by undesirable side effects such as sedation, bradycardia, and hypotension. Recently, the A2A receptor subtype emerged as a potential therapeutic attractive target in ischemia. Evidence suggests that A2A receptor has dual role: in a first phase of ischemia, it potentiates excitotoxicity, while hours and days after ischemia, A2A receptors on immune blood cells potentiate cell adhesion mechanisms and infiltration in the ischemic parenchyma. Consistently, the use of A2A receptor agonists/antagonists (administered at doses that do not modify blood pressure and heart rate) should be carefully evaluated in function of time after ischemia. Although much is still to be known about the role of A2B and A3 receptor subtypes in brain ischemia, most consistent information indicates their role in regulation of immunosuppression and inflammation.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy. Electronic address: alessia.melani@unifi.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Melani
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pugliese
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
authors.forename: Felicita
authors.initials: F
authors.lastname: Pedata
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D058905:Purinergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018047:Receptors, Purinergic P1 / Q000627:therapeutic use*
chemical_list: D058905:Purinergic Agents; D018047:Receptors, Purinergic P1
keywords: Adenosine; Adenosine receptor; Brain; Cerebral ischemia; Excitotoxicity; Neuroinflammation