ADORA2A and ischemia: Since A3R is known to have lower affinity for adenosine (Müller and Jacobson, 2011, but see Fredholm et al., 2001b) compared to A1R and A2AR, its activity may be relevant especially after acute brain insults, such as in ischemia and traumatic brain injury, when the extracellular level of adenosine dramatically increases (Fredholm, 2007).