Objective   To investigate the effect of adenosine A

2A

receptor deficiency on the ischemic neuronal injury and its potential mechanism.    Methods   Transient (2 h) cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. Adenosine A

2A

receptor knockout (A

2A

RKO) mice and their wild-type littermates (A

2A

RWT) were divided into 2-hour cerebral ischemia group

cerebral ischemia with 22-hour reperfusion group and cerebral ischemia with 46-hour reperfusion group. Cerebral infarction volume was measured by image analysis of brain sections stained with cresyl violet (CV). Brain water content was evaluated with the dry-wet weighing method. The expression of calbindin D-28k (CB) and aquaporin-4 (AQP4) in ischemic brain was determined with immunohistochemical methods.    Results   The cerebral infarction volumes in 2-hour cerebral ischemia group

cerebral ischemia with 22-hour reperfusion group and cerebral ischemia with 46-hour reperfusion group of A

2A

RKO mice were lesser than those in the corresponding groups of A

2A

RWT mice. Compared with A

2A

RWT mice

A

2A

RKO mice had more CB

lesser AQP4 expressions and lesser brain water contents.    Conclusion   Adenosine A

2A

receptor deficiency exerts the protection against ischemic brain injury both in the acute phase and reperfusion phase

and attenuates brain edema caused by cerebral ischemia

which may be due to the inhibition of intracellular calcium overload and AQP4 expression.