A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice

Extracellular adenosine critically modulates ischemic brain injury, at leas t in part through activation of the A(1) adenosine receptor. However, the r ole played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitatio ns, we explored the consequences of deleting the A(2A) adenosine receptor o n brain damage after transient focal ischemia. Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia ) did not differ between A(2A) receptor knock-out and wild-type littermates . The volume of cerebral infarction, as well as the associated neurological deficit induced by transient filament occlusion of the middle cerebral art ery, were significantly attenuated in A(2A) receptor knock-out mice. This n europrotective phenotype of A(2A) receptor-deficient mice was observed in d ifferent genetic backgrounds, confirming A(2A) receptor disruption as its c ause. Together with complimentary pharmacological studies, these data sugge st that A(2A) receptors play a prominent role in the development of ischemi c injury within brain and demonstrate the potential for anatomical and func tional neuroprotection against stroke by A(2A) receptor antagonists.