Background Adenosine is important in neonatal hypoxic ischemic brain damage regulating both vascular blood flow and inflammation. However, the role of the different receptor subtypes is still unclear.

Objective To investigate the effect of the different adenosine receptors during hypoxic ischemia.

Method Ligation of the carotid artery and subsequent hypoxia in 10% O₂ for 1 h in adenosine A1, A2A and A3 knockout mice. Behavioral changes were evaluated in open field and beam walking tests followed by morphological evaluation by cresyl violet and MAP-2 staining.

Results Our preliminary results show that the adenosine receptors play a protective role. A1 knockouts had a significantly larger morphological score and altered locomotion in the open field compared with wild type controls, indicating a protective effect of the A1 receptor. Moreover, both A2A and A3 receptor knockouts showed a tendency towards increased brain damage and significantly increased slips on the beam walk test as well as locomotor activity compared to wild type mice.

Conclusions The role of the different adenosine receptors has been debated and so far no data have been presented from all subtypes in the same model system. We show that A2A and A3 receptors have a protective effect and that the adenosine system is in fact a substantial contributor to the outcome after hypoxic ischemia in the newborn. Thus beneficial therapies may be developed by targeting the adenosine system.