POSTISCHEMIC ADMINISTRATION OF ADENOSINE AMINE CONGENER (ADAC) - ANALYSIS OF RECOVERY IN GERBILS

Although adenosine receptor-based treatment of cerebral ischemia and o ther neurodegenerative disorders has been frequently advocated, cardio vascular side effects and an uncertain therapeutic time window of such treatment have constituted major obstacles to clinical implementation . Therefore, we have investigated the neuroprotective effects of the a denosine A, receptor agonist adenosine amine congener (ADAC) injected after either 5 or 10 min ischemia at 100 mu g/kg. When the drug was ad ministered at either 6 or 12 h following 5 min forebrain ischemia, all animals were still alive on the 14th day after the occlusion. In both ADAC treated groups neuronal survival was approximately 85% vs. 50% i n controls. Administration of a single dose of ADAC at times 15 min to 12 h after 10 min ischemia resulted in a significant improvement of s urvival in animals injected either at 15 or 30 min, or at 1, 2, or 3 h after the insult. In all 10 min ischemia groups, administration of AD AC resulted in a significant protection of neuronal morphology and pre servation of microtubule associated protein 2 (MAP-2). However, postis chemic Morris' water maze tests revealed full preservation of spatial memory and learning ability in animals injected at 6 h. On the other h and, the performance of gerbils treated at 12 h postischemia was indis tinguishable from that of the controls. Administration of ADAC at 100 mu g/kg in non-ischemic animals did not result in bradycardia, hypoten sion, or hypothermia. The data indicate that when ADAC is used postisc hemically, the most optimal level of protection is obtained when drugs are given at 30 min to 6 h after the insult. Although the mechanisms involved in neuroprotective effects of adenosine A(1) receptor agonist s require further studies, the present results demonstrate the feasibi lity of their clinical applications.