Blocking the glycine-binding site of NMDA receptors prevents the progression of ischemic pathology induced by bilateral carotid artery occlusion in spontaneously hypertensive rats

This study was designed to investigate the participation of N-methyl-D-aspa rtate (NMDA) receptors in the progression of the pathology induced by bilat eral carotid artery occlusion (BCAo) in spontaneously hypertensive rats (SH Rs). We examined the effects of the selective NMDA receptor glycine-binding site antagonist SM-18400 on the mortality rate, deterioration of neurologi cal signs, and formation of brain edema in the SHR-BCAo model. SM-18400 (15 or 30 mg/kg) was administered via the tail vein immediately and 2 h after BCAo. Neurological signs were monitored continuously for 8 h after BCAo, an d the mortality rates were followed for 5 days. All SM-18400-treated animal s were still alive 5 h after BCAo, whereas 38% of the animals died in the v ehicle-treated group. The mortality rates of the SM-18400-treated groups we re still lower than those of the vehicle-treated group 5 days after BCAo. I n addition, SM-18400 markedly prevented the deterioration of neurological s igns. The water content of the telencephalon and diencephalon/mesencephalon in the vehicle-treated group, measured 3 h after BCAo, was significantly h igher than in the sham-operated group. SM-18400 significantly inhibited the increase in water content in both regions in a dose-dependent manner. Thes e findings suggest that NMDA receptors participate in the increase in the m ortality rate, deterioration of neurological signs, and formation of brain edema following ischemic brain damage in the SHR-BCAo model, and that SM-18 400 can prevent ischemic insults. (C) 2000 Elsevier Science B.V. All rights reserved.