By bolstering glutamate excitotoxicity and neuroinflammation, A2AR also contribute to synaptic and neuronal damage, as heralded by the neuroprotection afforded by the genetic or pharmacological blockade of A2AR in animal models of ischemia, traumatic brain injury, convulsions/epilepsy, repeated stress or Alzheimer’s or Parkinson’s diseases. This evidence concerns the gene ADORA2A and ischemia.