Antagonists and Spinal-Cord Ischemia Competitive NMDA Receptor
Authors: Follis, Fabrizio; Blisard, Karen; Varvitsiotis, Poseidon S.; Pett, Stuart B.; Temes, Tom; Wernly, Jorge A.
Source: Journal of Investigative Surgery, Volume 13, Number 2, 1 March 2000 , pp. 117-121(5)
Publisher: Informa Healthcare
Abstract:Ischemic neuronal death is associated with excitatory amino acid (EAA) release. Their action is mediated by N-methyl-D-aspartate (NMDA) receptors. Blockade of the receptors before the ischemic insult can decrease neuronal damage. 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 of 10 mu L saline, CGS, and CPP 10 mM solutions, in a randomized blinded fashion, and were subjected to balloon occlusion of the thoracic aorta. Proximal aortic pressure was lowered to a mean of 40 mm Hg by partial exsanguination. 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 in paraplegia in 50% of animals (P 50). In the chronic study, 24 rats divided 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 of the cord. In the acute study, the P 50 of CGS (10 min 48 s) and CPP (11 min 11 s) was longer than saline (10 min 27 s). In the chronic groups, analysis of variance of neurologic (p = .66) and histologic (p = .66) scores did not disclose differences between CGS, CPP, and saline. In conclusion, blockade of NMDA receptors with CPP or CGS may afford some protection for durations of occlusion around the P 0, but it is not beneficial when ischemic injury is more protracted.
Document Type: Research Article
Publication date: March 1, 2000