Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist.
Agonists of adenosine A1 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 micrograms/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 A1 receptor agonists as a clinically applicable acute treatment of brain ischemia. Recent development of neuroprotective adenosine A1 receptor agonists that are free of cardiovascular side effects supports such development.
Von Lubitz
D K
DK
NIH/NIDDK, Molecular Recognition Section, Bethesda, MD 20892 USA.
Beenhakker
M
M
Lin
R C
RC
Carter
M F
MF
Paul
I A
IA
Bischofberger
N
N
Jacobson
K A
KA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D005849:Gerbillinae; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists
D058906:Purinergic P1 Receptor Agonists; C106045:adenosine amine congener; D000241:Adenosine