新型非NMDA拮抗剂NBQX对大鼠缺血性海马CA1损伤的保护作用

Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.

作者信息

Diemer N H, Jørgensen M B, Johansen F F, Sheardown M, Honoré T

机构信息

Cerebral Ischemia Research Group, University of Copenhagen, Denmark.

出版信息

Acta Neurol Scand. 1992 Jul;86(1):45-9. doi: 10.1111/j.1600-0404.1992.tb08052.x.

DOI:10.1111/j.1600-0404.1992.tb08052.x

PMID:1325729

Abstract

Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.

摘要

在大鼠完全性短暂性脑缺血模型中对两种谷氨酸拮抗剂进行了测试。缺血10分钟后6天，海马CA1区锥体神经元的平均损失率为73%。给予AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）拮抗剂NBQX（2,3-二氢-6-硝基-7-氨磺酰基-苯并（F）喹喔啉），在缺血前、缺血后立即或缺血后1小时给药时，锥体神经元损失率分别降至1%、11%和15%。竞争性NMDA拮抗剂MK-801（地佐环平）在该模型中未提供保护作用。我们认为，AMPA受体转导机制因缺血而敏感化，并且用NBQX对CA1细胞主要谷氨酸能输入进行缺血后阻断可削弱“正常”缺血后兴奋性传递的有害作用。