Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A 1 receptor agonist

Abstract

Agonists of adenosine A 1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies determined the impact of cerebral ischemia and drug treatment on postischemic recovery of spatial memory. The present paper demonstrates that preischemic i.p. administration of adenosine amine congener (ADAC) at 100 μg/kg in gerbils results in a significant ( P < 0.05) reduction of postischemic mortality and hippocampal, cortical and striatal morbidity. Postischemic Morris' water maze tests show that preischemic treatment with ADAC also leads to a very significant ( P < 0.001) reduction of postischemic spatial memory loss. Our results indicate feasibility of further consideration of adenosine A 1 receptor agonists as a clinically applicable acute treatment of brain ischemia. Recent development of neuroprotective adenosine A 1 receptor agonists that are free of cardiovascular side effects supports such development.