This istradefylline-induced prevention of enhanced synaptic transmission following normoxic reperfusion strongly indicates that A2ARs play a crucial role in the elevation of extracellular glutamate concentrations via a presynaptic mechanism and in glutamate excitotoxicity via a postsynaptic A2AR-mediated modulation of AMPARs [24] in cerebral ischemia. The gene discussed is ADORA2A; the disease is brain ischemia.