The excitatory amino acid antagonist kynurenic acid administered after hypoxic-ischemia in neonatal rats offers neuroprotection

Abstract

The neuroprotective effect of kynurenic acid, an unspecific antagonist of excitatory amino acid receptors, was evaluated in a model of hypoxic-ischemia in neonatal rats. One-week-old rats were subjected to ligation of the left carotid artery and exposure to 7.7% O2/92.3% N2 for 2 h. Kynurenic acid (300 mg/kg) was administered i.p. immediately after the period of hypoxic-ischemia in one group (n = 32) and compared with saline-treated (n = 27). After 2 weeks the rats were sacrificed and the brain damage evaluated by comparing the weight of the lesioned and unlesioned hemispheres. In rats receiving kynurenic acid the reduction in weight of the lesioned hemisphere was 25.4 +/- 3.3% as compared to 37.8 +/- 3.6% in saline-treated controls (P less than 0.001). The results suggest that excitatory amino acids are involved in the development of postischemic damage in the immature brain.