Competitive NMDA receptor antagonists and spinal-cord ischemia

Ischemic neuronal death is associated with excitatory amino acid (EAA) rele ase. Their action is mediated by N-methyl-D-aspartate (NMDA) receptors. Blo ckade of the receptors before the ischemic insult can decrease neuronal dam age. Accordingly, we investigated the protective effect during spinal cord ischemia of two competitive antagonists, 4-(3-phosphonopropyl)-2-piperazine -carboxylic acid (CPP) and cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS). Male Sprague-Dawley rats underwent intrathecal administration o f 10 mu L saline, CGS, and CPP 10 mM solutions, in a randomized blinded fas hion, and were subjected to balloon occlusion of the thoracic aorta. Proxim al aortic pressure was lowered to a mean of 40 mm Hg by partial exsanguinat ion. In the acute protocol, 21 rats divided in 3 groups of 7 (saline, CPP, and CGS) were used to calculate the aortic occlusion time (AOT) resulting i n paraplegia in 50% of animals (P-50). In the chronic study, 24 rats divide d in 4 groups of 6 (saline, CPP, CGS, sham) underwent 12-min occlusion. The chronic animals were scored daily for 28 days and submitted to histology o f the cord. In the acute study, the P-50 of CGS (10 min 48 s) and CPP (11 m in 11 s) was longer than saline (10 min 27 s). In the chronic groups, analy sis of variance of neurologic (p = .66) and histologic (p = .66) scores did not disclose differences between CGS, CPP, and saline. In conclusion, bloc kade of NMDA receptors with CPP or CGS may afford some protection for durat ions of occlusion around the P-50, but it is not beneficial when ischemic i njury is more protracted.