Adenosine A2A antagonists are protective in in vivo and in vitro models of brain ischemia

Abstract

Event Abstract Back to Event Adenosine A2A antagonists are protective in in vivo and in vitro models of brain ischemia Felicita Pedata1*, Alessia Melani1, Anna M. Pugliese1, Sara Cipriani1 and Maria G. Giovannini1 1 University of Florence, Department of Preclinical and Clinical Pharmacology, Italy In the rat model of MCAo, the A2A antagonist, SCH58261, subchronically administered protects from neurological deficit and cortical and striatal damage evaluated 24 h after ischemia. In the first hour after ischemia, the A2A antagonist reduces glutamate outflow whereas 24 h after ischemia, A2A antagonist significantly reduces activation of p38 mitogen-activated protein kinase (MAPK) in microglial-activated cells. The A2A antagonist also reduces activation of JNK-MAPK in oligodendrocytes. In vitro results show that A2A receptors expressed on microglia activated BV-2 cells can directly contribute to phosphorylation of p38 MAPK. Data indicate that reduced excitotoxicity in the first hour after ischemia and reduced activation of p38 and JNK-MAPKs that are involved through transcriptional mechanisms in ischemic cell death, may underly protection by the A2A antagonist. The role of adenosine A2A receptor activation was also investigated in rat hippocampal slices during oxygen and glucose deprivation (OGD). Seven min OGD elicit an irreversible loss of fEPSP, invariably followed by the appearance of anoxic depolarization (AD), an unambiguous sign of neuronal damage. The selective adenosine A2A receptor antagonist ZM 241385 (100-500 nM) significantly prevented or delayed AD appearance and permitted a significant recovery of neurotransmission as well as a significant reduction of CA1 pyramidal neuronal damage assessed 1 hour staining with the PI (5 µg/ml) 2 hours from the end of OGD. Data indicate the delay of AD in the penumbral areas as a mechanism of protection by A2A antagonism against brain ischemic damage. Keywords: excitotoxicity, Glutamate, Ischemia, JNK-MAPK, Microglia Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Citation: Pedata F, Melani A, Pugliese AM, Cipriani S and Giovannini MG (2009). Adenosine A2A antagonists are protective in in vivo and in vitro models of brain ischemia. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.079 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Nov 2009; Published Online: 20 Nov 2009. * Correspondence: Felicita Pedata, University of Florence, Department of Preclinical and Clinical Pharmacology, Florence, Italy, felicita.pedata@unifi.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Felicita Pedata Alessia Melani Anna M Pugliese Sara Cipriani Maria G Giovannini Google Felicita Pedata Alessia Melani Anna M Pugliese Sara Cipriani Maria G Giovannini Google Scholar Felicita Pedata Alessia Melani Anna M Pugliese Sara Cipriani Maria G Giovannini PubMed Felicita Pedata Alessia Melani Anna M Pugliese Sara Cipriani Maria G Giovannini Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.