310 115. Simpson RE, O’Regan MH, Perkins LM et al (1992) Excitatory transmitter amino acid release from the ischemic rat cerebral cortex: effects of adenosine receptor agonists and antagonists. J Neurochem 58:1683–1690 116. Fiebich BL, Biber K, Lieb K et al (1996) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2A- receptors. Glia 18:152–160 117. Saura J, Angulo E, Ejarque A et al (2005) Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia. J Neurochem 95:919–929 118. Lee YC, Chien CL, Sun CN et al (2003) Characterization of the rat A2A adenosine receptor gene: a 4.8-kb promoter-proximal DNA fragment confers selective expression in the central nervous system. Eur J Neurosci 18:1786–1796 119. Nishizaki T, Nagai K, Nomura T et al (2002) A new neuro- modulatory pathway with a glial contribution mediated via A2A adenosine receptors. Glia 39:133–147 120. Pintor A, Galluzzo M, Grieco R et al (2004) Adenosine A2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors. J Neurochem 89:152–156 121. Irving EA, Barone FC, Reith AD et al (2000) Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat. Brain Res Mol Brain Res 77:65–75 122. Wu DC, Ye W, Che XM et al (2000) Activation of mitogen- activated protein kinases after permanent cerebral artery occlu- sion in mouse brain. J Cereb Blood Flow Metab 20:1320–1330 123. Barone FC, Irving EA, Ray AM et al (2001) Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Res Rev 21:129–145 124. Gao Y, Signore AP, Yin W et al (2005) Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N-terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway. J Cereb Blood Flow Metab 25:694–712 125. Kawasaki H, Morooka T, Shimohama S et al (1997) Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells. J Biol Chem 272:18518–18521 126. Trincavelli ML, Melani A, Guidi S et al (2007) Regulation of A2A adenosine receptor expression and functioning following perma- nent focal ischemia in rat brain. J Neurochem. DOI 10.1111/ j.1471-4159.2007.04990.x 127. Yu L, Huang Z, Mariani J et al (2004) Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat Med 10:1081–1087 128. Sheardown MJ, Knutsen LJS (1996) Unexpected neuroprotection observed with the adenosine A2A receptor agonist cgs 21680. Drug Dev Res 39:108 Purinergic Signalling (2007) 3:299–310 129. von Lubitz DK, Lin RC, Jacobson KA (1995) Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295– 302 130. Jones PA, Smith RA, Stone TW (1998) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85:229–237 131. Jones PA, Smith RA, Stone TW (1998) Protection against hippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800:328–335 132. Sitkovsky MV, Ohta A (2005) The ‘danger’ sensors that STOP the immune response: the A2 adenosine receptors? Trends Immunol 26:299–304 133. Mayne M, Fotheringham J, Yan HJ et al (2001) Adenosine A2A receptor activation reduces proinflammatory events and decreases cell death following intracerebral hemorrhage. Ann Neurol 49:727–735 134. Latini S, Corsi C, Pedata F et al (1995) The source of brain adenosine outflow during ischemia and electrical stimulation. Neurochem Int 27:239–244 135. Pugliese AM, Coppi E, Spalluto G et al (2006) A3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro. Br J Pharmacol 147:524–532 136. von Lubitz DK, Lin RC, Popik P et al (1994) Adenosine A3 receptor stimulation and cerebral ischemia. Eur J Pharmacol 263:59–67 137. Palmer TM, Benovic JL, Stiles GL (1995) Agonist-dependent phosphorylation and desensitization of the rat A3 adenosine receptor. Evidence for a G-protein-coupled receptor kinase- mediated mechanism. J Biol Chem 270:29607–29613 138. Trincavelli ML, Tuscano D, Marroni M et al (2002) A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down-regulation. Mol Pharmacol 62:1373–1384 139. Hentschel S, Lewerenz A, Nieber K (2003) Activation of A(3) receptors by endogenous adenosine inhibits synaptic transmis- sion during hypoxia in rat cortical neurons. Restor Neurol Neurosci 21:55–63 140. Fedorova IM, Jacobson MA, Basile A et al (2003) Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol 23:431–447 141. Chen GJ, Harvey BK, Shen H et al (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84:1848–1855 142. Pedata F, Pugliese AM, Coppi E et al (2007) Adenosine in the central nervous system: effects on neurotransmission and neuro- protection. Immunol Endocr Metab Agents Med Chem 7:304–321