MK-801 IS NEUROPROTECTIVE IN GERBILS WHEN ADMINISTERED DURING THE POST-ISCHAEMIC PERIOD
MK-801 IS NEUROPROTECTIVE IN GERBILS WHEN ADMINISTERED DURING THE POST-ISCHAEMIC PERIOD
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DOI：
10.1016/0306-4522(88)90040-1
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发表时间：
1988-06-01
期刊：
影响因子：
3.3
通讯作者：
WOODRUFF, GN
中科院分区：
文献类型：
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作者：
GILL, R;FOSTER, AC;WOODRUFF, GN
本文观察了非竞争性N-甲基-D-天冬氨酸受体拮抗剂(+)-5-甲基-10，11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺马来酸(MK-801)对沙土鼠海马神经元的保护作用。在双侧颈总动脉结扎所致的短暂性前脑缺血5min期间及之后的不同时间。MK-801单次给药1、3、10 mg/kg对缺血期间及缺血后24 h的海马CA1、CA2区锥体神经元有明显的保护作用。0.3 mg/kg的剂量在阻断期间有效，但在缺血后30分钟或2小时无保护作用。MK-801重复给药实验表明，1 mg/kg MK-801缺血后重复给药和1 mg/kg MK-801加0.3 mg/kg MK-801重复给药对小鼠有明显的保护作用。然而，0.3 mg/kg的MK-801在缺血后重复给药0.03 mg/kg并不具有神经保护作用。这些结果表明，MK-801在损伤后24小时给药，可保护海马神经元免受缺血所致的神经元变性。这些结果表明，MK-801在损伤后24小时给药，可保护海马神经元免受缺血所致的神经元变性。这些数据进一步证明，脑缺血后的治疗干预可以成功地预防神经退行性变事件，而缺血损伤后海马神经元的延迟退变是通过N-甲基-D-天冬氨酸受体介导的过程发生的。
The neuroprotective effects of the non-competitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) have been evaluated in the gerbil hippocampus when the drug was administered i.p. at various times during and after a 5 min period of transient forebrain ischaemia, induced by bilateral common carotid artery occlusion. A single dose of 1, 3 or 10 mg/kg of MK-801 gave significant protection of hippocampal CA1 and CA2 pyramidal neurons when administered during the occlusion and up to 24 h following the period of ischaemia. A dose of 0.3 mg/kg was effective when administered during the occlusion period but gave no protection at 30 min or 2 h post-ischaemia. Experiments in which MK-801 was administered in repeated doses indicated that significant protection was achieved with 1 mg/kg of MK-801 repeated post-ischaemically and with 1 mg/kg MK-801 supplemented with repeated doses of 0.3 mg/kg of MK-801. However, 0.3 mg/kg of MK-801 followed by repeated doses of 0.03 mg/kg administered post-ischaemically was not neuroprotective. These results indicate that MK-801 can protect hippocampal neurons from ischaemia-induced neuronal degeneration when it is administered up to 24 h after the insult. These results indicate that MK-801 can protect hippocampal neurons from ischaemia-induced neuronal degeneration when it is administered up to 24 h after the insult. These data provide further evidence that therapeutic intervention in the post-ischaemic period can successfully prevent neurodegenerative events, and that the delayed degeneration of hippocampal neurons following an ischaemic insult occurs by an N-methyl-D-aspartate receptor-mediated process.