Ischemic stroke is a complex pathology characterized by a sequence of events that evolve over time and space. It is the second leading cause of death and the main cause of adult long-term disability in developed countries. At the moment, there is no promising
pharmacotherapy for
acute ischemic stroke.
Adenosine receptors (A1, A2A, A2B, A3) are important targets for therapeutic implementation in the treatment of
stroke because extracellular
adenosine concentrations increase dramatically soon after
ischemia.
Adenosine receptors located both on central nervous system cells and on immune blood cells exert important roles during
ischemia. The neuroprotective role of
adenosine through A1 receptor subtype during
ischemia is accepted, but the use of selective A1 agonists is hampered by undesirable side effects such as sedation,
bradycardia, and
hypotension. Recently, the A2A receptor subtype emerged as a potential therapeutic attractive target in
ischemia. Evidence suggests that A2A receptor has dual role: in a first phase of
ischemia, it potentiates excitotoxicity, while hours and days after
ischemia, A2A receptors on immune blood cells potentiate cell adhesion mechanisms and infiltration in the ischemic parenchyma. Consistently, the use of A2A receptor agonists/antagonists (administered at doses that do not modify blood pressure and heart rate) should be carefully evaluated in function of time after
ischemia. Although much is still to be known about the role of A2B and A3 receptor subtypes in
brain ischemia, most consistent information indicates their role in regulation of immunosuppression and
inflammation.