A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice.
Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on 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 artery, were significantly attenuated in A(2A) receptor knock-out mice. This neuroprotective phenotype of A(2A) receptor-deficient mice was observed in different genetic backgrounds, confirming A(2A) receptor disruption as its cause. Together with complimentary pharmacological studies, these data suggest that A(2A) receptors play a prominent role in the development of ischemic injury within brain and demonstrate the potential for anatomical and functional neuroprotection against stroke by A(2A) receptor antagonists.
Chen
J F
JF
Molecular Neurobiology Laboratory, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. chenjf@helix.mgh.harvard.edu
Huang
Z
Z
Ma
J
J
Zhu
J
J
Moratalla
R
R
Standaert
D
D
Moskowitz
M A
MA
Fink
J S
JS
Schwarzschild
M A
MA
D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology / Q000503:physiopathology*; D020208:Brain Injury, Chronic / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D015698:Genomic Library; D006339:Heart Rate; D006439:Hemodynamics / Q000502:physiology*; D006720:Homozygote; D002546:Ischemic Attack, Transient / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000172:deficiency* / Q000235:genetics; D012039:Regional Blood Flow
D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1