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CNB-001 reduces paraplegia in rabbits following spinal cord ischemia

Spinal cord ischemia associated with trauma and surgical procedures including thoraco-abdominal aortic aneurysm repair and thoracic endovascular aortic repair results in devastating clinical deficits in patients. Because spinal cord ischemia is inadequately treated, we studied the effects of [4-((1E...

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Autores principales: Lapchak, Paul A., Boitano, Paul D., Bombien, Rene, Chou, Daisy, Knight, Margot, Muehle, Anja, Winkel, Mihaela Te, Khoynezhad, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788235/
https://www.ncbi.nlm.nih.gov/pubmed/31397359
http://dx.doi.org/10.4103/1673-5374.262598
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author Lapchak, Paul A.
Boitano, Paul D.
Bombien, Rene
Chou, Daisy
Knight, Margot
Muehle, Anja
Winkel, Mihaela Te
Khoynezhad, Ali
author_facet Lapchak, Paul A.
Boitano, Paul D.
Bombien, Rene
Chou, Daisy
Knight, Margot
Muehle, Anja
Winkel, Mihaela Te
Khoynezhad, Ali
author_sort Lapchak, Paul A.
collection PubMed
description Spinal cord ischemia associated with trauma and surgical procedures including thoraco-abdominal aortic aneurysm repair and thoracic endovascular aortic repair results in devastating clinical deficits in patients. Because spinal cord ischemia is inadequately treated, we studied the effects of [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol)] (CNB-001), a novel curcumin-based compound, in a rabbit SCI model. CNB-001 is known to inhibit human 5-lipoxygenase and 15-lipoxygenase and reduce the ischemia-induced inflammatory response. Moreover, CNB-001 can reduce the level of oxidative stress markers and potentiate brain-derived neurotrophic factor and brain-derived neurotrophic factor receptor signaling. The Tarlov scale and quantal analysis technique results revealed that CNB-001 administered as an intravenous dose (bolus) 30 minutes prior to spinal cord ischemia improved the behaviors of female New Zealand White rabbits. The improvements were similar to those produced by the uncompetitive N-methyl-D-aspartate receptor antagonist memantine. At 48 hours after aortic occlusion, there was a 42.7% increase (P < 0.05) in tolerated ischemia duration (n = 14) for rabbits treated with CNB-001 (n = 16), and a 72.3% increase for rabbits treated with the positive control memantine (P < 0.05) (n = 23) compared to vehicle-treated ischemic rabbits (n = 22). CNB-001 is a potential important novel treatment for spinal cord ischemia induced by aortic occlusion. All experiments were approved by the CSMC Institutional Animal Care and Use Committee (IACUC #4311) on November 1, 2012.
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spelling pubmed-67882352019-10-16 CNB-001 reduces paraplegia in rabbits following spinal cord ischemia Lapchak, Paul A. Boitano, Paul D. Bombien, Rene Chou, Daisy Knight, Margot Muehle, Anja Winkel, Mihaela Te Khoynezhad, Ali Neural Regen Res Research Article Spinal cord ischemia associated with trauma and surgical procedures including thoraco-abdominal aortic aneurysm repair and thoracic endovascular aortic repair results in devastating clinical deficits in patients. Because spinal cord ischemia is inadequately treated, we studied the effects of [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol)] (CNB-001), a novel curcumin-based compound, in a rabbit SCI model. CNB-001 is known to inhibit human 5-lipoxygenase and 15-lipoxygenase and reduce the ischemia-induced inflammatory response. Moreover, CNB-001 can reduce the level of oxidative stress markers and potentiate brain-derived neurotrophic factor and brain-derived neurotrophic factor receptor signaling. The Tarlov scale and quantal analysis technique results revealed that CNB-001 administered as an intravenous dose (bolus) 30 minutes prior to spinal cord ischemia improved the behaviors of female New Zealand White rabbits. The improvements were similar to those produced by the uncompetitive N-methyl-D-aspartate receptor antagonist memantine. At 48 hours after aortic occlusion, there was a 42.7% increase (P < 0.05) in tolerated ischemia duration (n = 14) for rabbits treated with CNB-001 (n = 16), and a 72.3% increase for rabbits treated with the positive control memantine (P < 0.05) (n = 23) compared to vehicle-treated ischemic rabbits (n = 22). CNB-001 is a potential important novel treatment for spinal cord ischemia induced by aortic occlusion. All experiments were approved by the CSMC Institutional Animal Care and Use Committee (IACUC #4311) on November 1, 2012. Wolters Kluwer - Medknow 2019-08-07 /pmc/articles/PMC6788235/ /pubmed/31397359 http://dx.doi.org/10.4103/1673-5374.262598 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Lapchak, Paul A.
Boitano, Paul D.
Bombien, Rene
Chou, Daisy
Knight, Margot
Muehle, Anja
Winkel, Mihaela Te
Khoynezhad, Ali
CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title_full CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title_fullStr CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title_full_unstemmed CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title_short CNB-001 reduces paraplegia in rabbits following spinal cord ischemia
title_sort cnb-001 reduces paraplegia in rabbits following spinal cord ischemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788235/
https://www.ncbi.nlm.nih.gov/pubmed/31397359
http://dx.doi.org/10.4103/1673-5374.262598
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