Competitive NMDA receptor antagonists and spinal-cord ischemia

Fabrizio Follis, Karen Blisard, Poseidon S. Varvitsiotis, Stuart B. Pett, Tom Temes, Jorge A. Wernly

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 μL 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 mmHg 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 (P50). 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 P50 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 P50, but it is not beneficial when ischemic injury is more protracted.

Original languageEnglish
Pages (from-to)117-121
Number of pages5
JournalJournal of Investigative Surgery
Volume13
Issue number2
Publication statusPublished - Mar 2000

Fingerprint

Spinal Cord Ischemia
N-Methyl-D-Aspartate Receptors
Exsanguination
Balloon Occlusion
Excitatory Amino Acids
Paraplegia
Carboxylic Acids
Thoracic Aorta
Nervous System
Sprague Dawley Rats
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
Histology
Analysis of Variance
Arterial Pressure
Wounds and Injuries

Keywords

  • Ischemia
  • N-methylaspartate
  • Paraplegia
  • Spinal cord

ASJC Scopus subject areas

  • Surgery

Cite this

Follis, F., Blisard, K., Varvitsiotis, P. S., Pett, S. B., Temes, T., & Wernly, J. A. (2000). Competitive NMDA receptor antagonists and spinal-cord ischemia. Journal of Investigative Surgery, 13(2), 117-121.

Competitive NMDA receptor antagonists and spinal-cord ischemia. / Follis, Fabrizio; Blisard, Karen; Varvitsiotis, Poseidon S.; Pett, Stuart B.; Temes, Tom; Wernly, Jorge A.

In: Journal of Investigative Surgery, Vol. 13, No. 2, 03.2000, p. 117-121.

Research output: Contribution to journalArticle

Follis, F, Blisard, K, Varvitsiotis, PS, Pett, SB, Temes, T & Wernly, JA 2000, 'Competitive NMDA receptor antagonists and spinal-cord ischemia', Journal of Investigative Surgery, vol. 13, no. 2, pp. 117-121.
Follis F, Blisard K, Varvitsiotis PS, Pett SB, Temes T, Wernly JA. Competitive NMDA receptor antagonists and spinal-cord ischemia. Journal of Investigative Surgery. 2000 Mar;13(2):117-121.
Follis, Fabrizio ; Blisard, Karen ; Varvitsiotis, Poseidon S. ; Pett, Stuart B. ; Temes, Tom ; Wernly, Jorge A. / Competitive NMDA receptor antagonists and spinal-cord ischemia. In: Journal of Investigative Surgery. 2000 ; Vol. 13, No. 2. pp. 117-121.
@article{81c34d0dda8647bfb4b601b431d89773,
title = "Competitive NMDA receptor antagonists and spinal-cord ischemia",
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 μL 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 mmHg 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 (P50). 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 P50 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 P50, but it is not beneficial when ischemic injury is more protracted.",
keywords = "Ischemia, N-methylaspartate, Paraplegia, Spinal cord",
author = "Fabrizio Follis and Karen Blisard and Varvitsiotis, {Poseidon S.} and Pett, {Stuart B.} and Tom Temes and Wernly, {Jorge A.}",
year = "2000",
month = "3",
language = "English",
volume = "13",
pages = "117--121",
journal = "Journal of Investigative Surgery",
issn = "0894-1939",
publisher = "Taylor and Francis Ltd.",
number = "2",

}

TY - JOUR

T1 - Competitive NMDA receptor antagonists and spinal-cord ischemia

AU - Follis, Fabrizio

AU - Blisard, Karen

AU - Varvitsiotis, Poseidon S.

AU - Pett, Stuart B.

AU - Temes, Tom

AU - Wernly, Jorge A.

PY - 2000/3

Y1 - 2000/3

N2 - 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 μL 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 mmHg 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 (P50). 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 P50 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 P50, but it is not beneficial when ischemic injury is more protracted.

AB - 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 μL 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 mmHg 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 (P50). 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 P50 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 P50, but it is not beneficial when ischemic injury is more protracted.

KW - Ischemia

KW - N-methylaspartate

KW - Paraplegia

KW - Spinal cord

UR - http://www.scopus.com/inward/record.url?scp=0034054131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034054131&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 117

EP - 121

JO - Journal of Investigative Surgery

JF - Journal of Investigative Surgery

SN - 0894-1939

IS - 2

ER -