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CNB-001 reduces paraplegia in rabbits following spinal cord ischemia

Neural Regeneration Research 2019年第12期14卷 2192-2198页

作者： Paul A. Lapchak Paul D. Boitano Rene Bombien daisy chou Margot Knight Anja Muehle Mihaela Te Winkel Ali Khoynezhad Neurocore LLC Pomona CA USA Department of Surgery Memorial Care Health System Long Beach CA USA

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-((1 E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1 H-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.

关键词： curcumin analog spinal cord injury spinal cord ischemia thoraco-abdominal aortic aneurysm thoracic endovascular aortic repair motor function neuroprotection neurorepair

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