Hara H, Onodera H, Kogure K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Brain Res Bull. 1992 Nov;29(5):659-65. doi: 10.1016/0361-9230(92)90135-k.
The effects of dizocilipine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor/channel antagonist, were tested on the dysfunction of neurotransmitter and signal transduction systems and morphological damage 7 days after transient forebrain ischemia in gerbils. Neurotransmitter system (adenosine A1, muscarinic cholinergic receptor) and signal transduction system (inositol 1,4,5-trisphosphate receptor: IP3, protein kinase C: PKC, L-type calcium channels) binding sites were mapped by in vitro quantitative receptor autoradiography. All ligands used in the present study decreased significantly in the CA1 subfield 7 days after ischemia. In normothermic animals, pretreatment with MK-801 failed to protect against decreased receptor binding in the hippocampus 7 days after ischemia. Moreover, in a morphological study, pre- and posttreatment of MK-801 failed to show protective effects against ischemic neuronal damage. On the other hand, pretreatment of MK-801, without maintaining body temperature, prevented the neuronal death of CA1 subfield 7 days after ischemia. These results weaken the hypothesis that NMDA receptor/channel may play a pivotal role in the pathogenesis of neuronal damage after transient forebrain ischemia.
在沙土鼠短暂性前脑缺血7天后，对非竞争性N-甲基-D-天冬氨酸（NMDA）受体/通道拮抗剂马来酸氯氮平（MK-801）对神经递质和信号转导系统功能障碍以及形态学损伤的影响进行了测试。通过体外定量受体放射自显影对神经递质系统（腺苷A1、毒蕈碱胆碱能受体）和信号转导系统（肌醇1,4,5-三磷酸受体：IP3、蛋白激酶C：PKC、L型钙通道）结合位点进行定位。本研究中使用的所有配体在缺血7天后在CA1亚区均显著减少。在常温动物中，MK-801预处理未能防止缺血7天后海马体中受体结合减少。此外，在一项形态学研究中，MK-801的预处理和后处理均未显示出对缺血性神经元损伤的保护作用。另一方面，在不维持体温的情况下，MK-801预处理可防止缺血7天后CA1亚区的神经元死亡。这些结果削弱了NMDA受体/通道可能在短暂性前脑缺血后神经元损伤发病机制中起关键作用的假说。
