THE N-METHYL-D-ASPARTATE ANTAGONIST, MK-801, FAILS TO PROTECT AGAINST NEURONAL DAMAGE CAUSED BY TRANSIENT, SEVERE FOREBRAIN ISCHEMIA IN ADULT-RATS

被引:0
|
作者
BUCHAN, A
LI, H
PULSINELLI, WA
机构
[1] CORNELL UNIV,MED CTR,DEPT NEUROL & NEUROSCI,CEREBROVASC DIS RES CTR,1300 YORK AVE,NEW YORK,NY 10021
[2] CORNELL UNIV,MED CTR,DEPT NEUROL & NEUROSCI,RAYMOND & BEVERLY SACKLER FDN INC,NEW YORK,NY 10021
[3] UNIV WESTERN ONTARIO HOSP,DEPT CLIN NEUROL SCI,ROBARTS RES INST,CEREBRAL ISCHEMIA LAB,LONDON N6A 5A5,ONTARIO,CANADA
来源
JOURNAL OF NEUROSCIENCE | 1991年 / 11卷 / 04期
关键词
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA 1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA 1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p < 0.001) dead CA 1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury. Despite doses of MK-801 that produced marked behavioral abnormalities in the rats, no protection against ischemic injury to CA 1 neurons was observed with any of the treatment paradigms. These data fail to support a singular role for the NMDA receptor/channel in the pathogenesis of injury to neurons from even brief periods of severe ischemia.
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页码:1049 / 1056
页数:8
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