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The neuromodulator adenosine accumulates extracellularly during ischaemia and activates four metabotropic receptors: A<jats:sub>1<\/jats:sub>, A<jats:sub>2A<\/jats:sub>, A<jats:sub>2B<\/jats:sub> and A<jats:sub>3<\/jats:sub>. Striatal medium spiny neurons (MSNs) express high levels of A<jats:sub>2A<\/jats:sub> receptors and are particularly vulnerable to ischaemic insults. A<jats:sub>2A<\/jats:sub> Receptor blockade reduces acute striatal post\u2010ischaemic damage but the cellular mechanisms involved are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We performed patch\u2010clamp recordings of MSNs in rat striatal slices subjected to oxygen and glucose deprivation (OGD) to investigate the effects of A<jats:sub>2A<\/jats:sub> receptor ligands or ion channel blockers on AD and OGD\u2010induced ionic imbalance, measured as a positive shift in E<jats:sub>rev<\/jats:sub> of ramp currents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Our data indicate that the A<jats:sub>2A<\/jats:sub> receptor antagonist SCH58261 (10\u00a0\u03bcM) significantly attenuated ionic imbalance and AD appearance in MSNs exposed to OGD. The K<jats:sup>+<\/jats:sup> channel blocker Ba<jats:sup>2+<\/jats:sup> (2\u00a0mM) or the Na<jats:sup>+<\/jats:sup> channel blocker tetrodotoxin (1\u00a0\u03bcM) exacerbated and attenuated, respectively, OGD\u2010induced changes.<\/jats:p><jats:p>Spontaneous excitatory post\u2010synaptic current (sEPSC) analysis in MSNs revealed that the A<jats:sub>2A<\/jats:sub> receptor agonist CGS21680 (1\u00a0\u03bcM) prevented OGD\u2010induced decrease of sEPSCs within the first 5\u00a0min of the insult, an effect shared by the K<jats:sup>+<\/jats:sup> channel blocker Ba<jats:sup>2+<\/jats:sup>, indicating facilitated glutamate release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Adenosine, released during striatal OGD, activates A<jats:sub>2A<\/jats:sub> receptors that may exacerbate OGD\u2010induced damage through K<jats:sup>+<\/jats:sup> channel inhibition. Our results could help to develop A<jats:sub>2A<\/jats:sub> receptor\u2010selective therapeutic tools for the treatment of brain ischaemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15922","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T03:03:09Z","timestamp":1657594989000},"page":"4844-4856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Selective block of adenosine A<sub>2A<\/sub> receptors prevents ischaemic\u2010like effects induced by oxygen and glucose deprivation in rat medium spiny neurons"],"prefix":"10.1111","volume":"179","author":[{"given":"Elisabetta","family":"Coppi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair J.","family":"Gibb","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Physiology and Pharmacology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15542"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15543"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15539"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.5539-03.2004"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3613"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.167"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(77)90646-1"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00257.2018"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.13.1.171"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.05.035"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00816.2009"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/pl00005355"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.588757"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200637024"},{"issue":"2","key":"e_1_2_12_18_1","first-page":"537","article-title":"Extracellular adenosine concentrations in hippocampal brain\u2010slices and the tonic inhibitory modulation of evoked excitatory responses","volume":"268","author":"Dunwiddie T. 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