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The Journal of Neuroscience, November 1, 1999, 19(21):9192-9200

A_2A Adenosine Receptor Deficiency Attenuates Brain Injury Induced by Transient Focal Ischemia in Mice

Jiang-Fan Chen¹, Zhihong Huang², Jianya Ma², JinMin Zhu², Rosario Moratalla³, David Standaert³, Michael A. Moskowitz², J. Stephen Fink¹, and Michael A. Schwarzschild¹

¹ Molecular Neurobiology Laboratory, ² Stroke and Neurovascular Regulation Laboratory, and ³ Neurology Research Laboratory, Department of Neurology and Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A₁ 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.

Key words: A_2A adenosine receptor; ischemia; stroke; purine receptor; knock-out; neuroprotection

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19219192-09$05.00/0

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