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

被引:37
作者
VonLubitz, DKJE
Beenhakker, M
Lin, RCS
Carter, MF
Paul, IA
Bischofberger, N
Jacobson, KA
机构
[1] MED COLL PENN & HAHNEMANN UNIV, DEPT ANAT & NEUROBIOL, PHILADELPHIA, PA 19102 USA
[2] UNIV MISSISSIPPI, MED CTR, LAB NEUROBEHAV PHARMACOL & IMMUNOL, JACKSON, MS 39216 USA
[3] GILEAD SCI INC, FOSTER CITY, CA 94404 USA
关键词
cerebral ischemia; adenosine receptor; spatial memory; water maze; (gerbil);
D O I
10.1016/0014-2999(96)00101-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Agonists of adenosine A(1) receptors have been frequently proposed as candidate, 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. Thr present paper demonstrates that preischemic i.p. administration of adenosine amine congener(ADAC) at 100 mu g/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.
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页码:43 / 48
页数:6
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