Lahtinen H, Ylinen A, Hyvönen M, Sirviö J, Miettinen R, Riekkinen P J
Department of Neurology, A.I. Virtanen Institute, University of Kuopio, Finland.
Brain Res. 1993 Oct 15;625(1):93-9. doi: 10.1016/0006-8993(93)90141-9.
Sustained electrical stimulation of the perforant pathway (PP) was used to induce hippocampal seizures in conscious rats. About 4.5 h prior to stimulation, animals were given i.p. injections of either saline or CGP 39551 (10 mg/kg), a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. When tested 2 weeks later in water maze, the saline pretreated rats showed a severe impairment in spatial learning whereas the animals treated with CGP 39551 had the same escape latencies as the non-stimulated controls. Histological evaluation of cellular degeneration revealed that the number of somatostatin-immunoreactive (SOM-IR) neurons in both stimulated groups was reduced almost equally, but in the CGP 39551 treated animals pyramidal cell damage was partly protected. However, in contrast to the placebo group, NMDA-sensitive [3H]glutamate binding in strata radiatum and oriens of the CA1 area was not significantly reduced in the CGP 39551 group. Thus, the present results suggest that the CGP 39551 treatment was able to protect against the delayed phase of the excitotoxic cell damage, and that the preservation of NMDA receptors partly accounts for the good learning ability of the CGP 39551 pretreated, PP-stimulated rats.
采用持续电刺激穿通通路（PP）诱导清醒大鼠海马癫痫发作。在刺激前约4.5小时，给动物腹腔注射生理盐水或CGP 39551（10毫克/千克），后者是N-甲基-D-天冬氨酸（NMDA）受体的竞争性拮抗剂。两周后在水迷宫中进行测试时，预先用生理盐水处理的大鼠在空间学习方面表现出严重受损，而用CGP 39551处理的动物的逃避潜伏期与未受刺激的对照组相同。细胞变性的组织学评估显示，两个受刺激组中生长抑素免疫反应性（SOM-IR）神经元的数量几乎同等减少，但在CGP 39551处理的动物中，锥体细胞损伤得到了部分保护。然而，与安慰剂组不同，CGP 39551组CA1区辐射层和原层中NMDA敏感的[3H]谷氨酸结合并未显著减少。因此，目前的结果表明，CGP 39551处理能够预防兴奋性毒性细胞损伤的延迟期，并且NMDA受体的保留部分解释了CGP 39551预处理的PP刺激大鼠良好的学习能力。
