Block by N6-L-phenylisopropyl-adenosine of the electrophysiological and morphological correlates of hippocampal ischaemic injury in the gerbil.

1. The effects of the mixed A1 and A2 adenosine receptor agonist N6-L-phenyl-isopropyladenosine (L-PIA) were tested on ischaemia-induced hippocampal neuronal injury in gerbils subjected to 5-min bilateral carotid occlusion. For comparison, the effects of the selective A2 adenosine receptor agonist, CGS 21680 were tested. 2. Five-min bilateral carotid occlusion produced within 1 week an irreversible suppression of the CA1, but not of the dentate extracellular electrical somatic responses, in 30% of gerbil hippocampal slices with respect to controls. In addition, a significant reduction occurred in the density of CA1 hippocampal pyramidal neurones but not of dentate granule cells with respect to controls. 3. Injection 1 h before or after bilateral carotid occlusion of L-PIA (0.8-1.5 mg kg-1, i.p.) but not of CGS 21680 (5 mg kg-1, i.p.), significantly prevented the irreversible disappearance of the CA1 extracellular electrical somatic responses with respect to controls. In addition, the CA1 pyramidal neuronal loss was also prevented. 4. The results show that activation of A1 adenosine receptors is able to prevent or block the electrophysiological and morphological correlates of hippocampal neuronal injury after global ischaemia in the gerbil, suggesting that adenosine receptor agonists might have a useful role in the treatment of neuronal functional and anatomical injury due to ischaemia.