Effect of glycine and glycine receptor antagonists on NMDA-induced brain injury

Abstract

In postnatal day 7 rats, a unilateral intrastriatal injection of 12.5 nmol of (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), Pn=6) reduced average % damage from 17.1+/-1.6% (n=15) to 3.0+/-0.6%, P<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.