Kass I S, Chambers G, Cottrell J E
Anesthesiology Department, State University of New York, Brooklyn 11203.
Exp Neurol. 1989 Feb;103(2):116-22. doi: 10.1016/0014-4886(89)90072-1.
The effect of the N-methyl-D-aspartate antagonists, aminophosphonovaleric acid and MK-801, on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from either the dentate granule cells or the CA1 pyramidal cells and the amplitude of this spike was compared before and 60 min following anoxia. After 10 min of anoxia the dentate granule cells recovered to 16 +/- 7% (mean +/- SE) of their preanoxic level when untreated and to 54 +/- 15% when treated with aminophosphonovaleric acid (APV). In slices treated with MK-801 the population spikes recorded from dentate granule cells recovered to 85 +/- 4% of their preanoxic level after 10 min of anoxia. Untreated CA1 pyramidal cells recovered to 8 +/- 3% of their preanoxic amplitude after 5 min of anoxia; they recovered to 59 +/- 6% when treated with MK-801 and 31 +/- 13% when treated with APV. The recovery of slices treated with the drugs was significantly different from that of untreated slices. ATP levels were measured in both the dentate and the CA1 region of slices. ATP in both regions fell less during anoxia when the slices were pretreated with either APV or MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801 in dentate tissue after 10 min of anoxia and with MK-801 in CA1 tissue after 5 min of anoxia. This reduced fall in ATP during anoxia was accompanied by better physiological recovery after anoxia. We conclude that these NMDA antagonists provide protection against anoxic damage to dentate granule and CA1 pyramidal cells in this in vitro hippocampal preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
使用海马脑片制备技术，研究了N-甲基-D-天冬氨酸拮抗剂（氨磷戊酸和MK-801）对缺氧后不可逆传递损失的影响。记录齿状颗粒细胞或CA1锥体细胞的群体峰电位，并比较缺氧前和缺氧60分钟后的峰电位幅度。缺氧10分钟后，未处理的齿状颗粒细胞恢复到缺氧前水平的16±7%（平均值±标准误），用氨磷戊酸（APV）处理后恢复到54±15%。在用MK-801处理的脑片中，缺氧10分钟后，从齿状颗粒细胞记录的群体峰电位恢复到缺氧前水平的85±4%。未处理的CA1锥体细胞在缺氧5分钟后恢复到缺氧前幅度的8±3%；用MK-801处理后恢复到59±6%，用APV处理后恢复到31±13%。用药物处理的脑片的恢复情况与未处理的脑片有显著差异。测量了脑片齿状区和CA1区的ATP水平。当脑片用APV或MK-801预处理时，两个区域的ATP在缺氧期间下降较少。药物处理和未处理组织之间的这些差异在APV和MK-801处理组中具有显著性。在缺氧10分钟后的齿状组织中，APV和MK-801处理组之间存在显著差异；在缺氧5分钟后的CA1组织中，MK-801处理组之间存在显著差异。缺氧期间ATP下降的减少伴随着缺氧后更好的生理恢复。我们得出结论，在这种体外海马制备中，这些NMDA拮抗剂可保护齿状颗粒细胞和CA1锥体细胞免受缺氧损伤。（摘要截短至250字）
