Uckele J E, McDonald J W, Johnston M V, Silverstein F S
Department of Pediatrics, University of Michigan, Ann Arbor.
Neurosci Lett. 1989 Dec 15;107(1-3):279-83. doi: 10.1016/0304-3940(89)90831-8.
In postnatal day 7 rats, a unilateral intrastriatal injection of 12.5 nmol of N-methyl-D-aspartate (NMDA) reproducibly injures the ipsilateral striatum, adjacent hippocampus and overlying cortex. The severity of injury can be quantified by comparing cerebral hemisphere weights in animals sacrificed 5 days after the injection. Co-injection of NMDA and the glycine receptor antagonists kynurenic acid (KYN) or 7-chlorokynurenic acid (7-CKA) reduced the severity of NMDA-induced damage in a dose-dependent fashion. One hundred nmol of KYN with 12.5 nmol of NMDA reduced average % damage from 19.3 +/- 0.9% (n = 9) to 2.3 +/- 0.5% (n = 6), P less than 0.001, ANOVA. Co-injection of 40 nmol of 7-CKA with 12.5 nmol of NMDA (n = 6) reduced average % damage from 17.1 +/- 1.6% (n = 15) to 3.0 +/- 0.6%, P less than 0.001, ANOVA. Concurrent injection of 1000 nmol glycine with 5 nmol NMDA did not increase the extent of NMDA-induced damage. Our results demonstrate that glycine receptor antagonists attenuate NMDA-induced brain injury in vivo.
在出生后第7天的大鼠中，向纹状体内单侧注射12.5纳摩尔的N-甲基-D-天冬氨酸（NMDA）可重复性地损伤同侧纹状体、相邻海马体和上方的皮质。损伤的严重程度可通过比较注射后5天处死的动物的大脑半球重量来量化。将NMDA与甘氨酸受体拮抗剂犬尿喹啉酸（KYN）或7-氯犬尿喹啉酸（7-CKA）共同注射，可剂量依赖性地降低NMDA诱导的损伤严重程度。100纳摩尔的KYN与12.5纳摩尔的NMDA共同注射可使平均损伤百分比从19.3±0.9%（n = 9）降至2.3±0.5%（n = 6），方差分析，P<0.001。40纳摩尔的7-CKA与12.5纳摩尔的NMDA共同注射（n = 6）可使平均损伤百分比从17.1±1.6%（n = 15）降至3.0±0.6%，方差分析，P<0.001。1000纳摩尔甘氨酸与5纳摩尔NMDA同时注射并未增加NMDA诱导的损伤程度。我们的结果表明，甘氨酸受体拮抗剂可减轻体内NMDA诱导的脑损伤。
