Deletion of the adenosine A1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro

Extracellular adenosine is dramatically increased during cerebral ischaemia and is considered to be neuroprotective due to its inhibitory effect on synaptic transmission mediated by the adenosine A(1) receptor (A(1)R). We investigated the importance of the A(1)R in a mouse model of global ischaemia and in a murine hippocampal slice culture model of in vitro ischaemia, using mice with the A(1)R gene deleted. In brains from mice lacking the A(1)R, damage induced by global ischaemia was similar to that in wild-type animals. In contrast, treatment with a selective A(1)R antagonist [8-cyclo-pentyl theophylline (8-CPT)], administered before the ischaemic insult in naive wild-type mice, exacerbated the neuronal damage following global ischaemia. Although the inhibitory action of adenosine on excitatory neurotransmission in hippocampal slices was lost in A(1)R knockout mice, there was no difference in damage between slices from wild-type and knockout mice after in vitro ischaemia. The results suggest that some effects of the A(1)R are compensated for in knockout animals.