中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (12): 2192-2198.doi: 10.4103/1673-5374.262598

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

姜黄素化合物CNB-001对主动脉阻塞致脊髓缺血的神经保护

  

  • 出版日期:2019-12-15 发布日期:2019-12-15

CNB-001 reduces paraplegia in rabbits following spinal cord ischemia

Paul A. Lapchak 1 , Paul D. Boitano 2 , Rene Bombien 2 , Daisy Chou 2 , Margot Knight 2 , Anja Muehle 2 , Mihaela Te Winkel 2 , Ali Khoynezhad 2   

  1. 1 Neurocore LLC, Pomona, CA, USA
    2 Department of Surgery, Memorial Care Health System, Long Beach, CA, USA
  • Online:2019-12-15 Published:2019-12-15
  • Contact: Paul A. Lapchak, PhD, FAHA, palapchak@gmail.com.

摘要:

新型姜黄素化合物CNB-001可减轻缺血诱导的炎症和氧化应激反应,但其对脊髓缺血的神经保护作用尚待进一步研究。实验在主动脉阻塞建立脊髓缺血兔模型前30min静脉内注射CNB-001或阳性对照非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚。CNB-001或美金刚干预后,耐受缺血持续时间明显延长,Tarlov评分评估的运动功能明显改善,且两种药物作用相当。说明CNB-001对减轻主动脉阻塞引起的缺血性脊髓损伤更有作用。

orcid: 0000-0003-4413-7554(Paul A. Lapchak)

关键词: 姜黄素类似物, 脊髓损伤, 脊髓缺血, 胸腹主动脉瘤, 胸主动脉的腔内修复, 运动功能, 神经保护, 神经修复

Abstract:

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.

Key words: curcumin analog, spinal cord injury, spinal cord ischemia, thoraco-abdominal aortic aneurysm, thoracic endovascular aortic repair, motor function, neuroprotection, neurorepair