Event Abstract

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

  • 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

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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