中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (8): 1208-1211.doi: 10.4103/1673-5374.189164

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

他莫昔芬:FDA批准的对脊髓损伤恢复具有神经保护作用的药物

  

  • 出版日期:2016-08-31 发布日期:2016-08-31
  • 基金资助:
    该研究项目由以下机构提供了部分支持:COBRE(P20-GM103642,MBRS-RISE计划(R25 GM061838),NIH-MARC(5T34GM007821-35)和RCMI计划(5G12MD007600)。

Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

Jennifer M. Colón, Jorge D. Miranda*   

  1. Department of Physiology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA
  • Online:2016-08-31 Published:2016-08-31
  • Contact: Jorge D. Miranda, Ph.D., jorge.miranda3@upr.edu.
  • Supported by:
    The project was partially supported by COBRE (P20-GM103642), the MBRS-RISE Program (R25 GM061838), NIH-MARC (5T34GM007821-35) and the RCMI program (5G12MD007600).

摘要:

文章报导了对使用他莫昔芬治疗脊髓损伤雌性大鼠的研究,他莫昔芬是联邦药物管理局的批准药物,通过有利于神经元存活、保护髓鞘和轴突进而发挥保护作用,这种治疗方式同时也有利于运动功能的恢复。这些对中枢神经系统病症的积极实验结果表示,他莫昔芬,目前作用于乳腺癌治疗药物对脊髓损伤是有效的。他们的数据和其他研究者得到的结果表明,他莫昔芬可发挥抗氧化、抗细胞凋亡、抗胶质增生和抗炎作用,同时降低脑和脊髓屏障渗透性,在多种脊髓损伤模型实验中可增加白质幸免组织。这一FDA批准的药物是对中枢神经系统创伤十分有益。在这个时刻,需要研究他莫昔芬介导的神经保护作用机制,并让它可以最大限度地发挥其对中枢神经系统损伤和病变的临床应用。他们认为多年来科学家们始终致力于研究可以扭转和恢复脊髓损的治疗策略。针对脊髓损伤的治疗干预方法应该考虑内皮细胞、神经元、星形胶质细胞、小胶质细胞和少突胶质细胞在局部和近端对病变部位的动态影响以及对炎症细胞的影响。由于脊髓损伤是一种多因素事件,有必要开发多活性药物来治疗这种疾病,这中开发策略将针对被脊髓损伤激活的多个事件。

orcid: 0000-0001-7705-1111 (Jorge D. Miranda)

Abstract: Spinal cord injury (SCI) is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, in?ammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the benefcial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-in?ammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the feld.

Key words: selective estrogen receptor modulator, trauma, antioxidant, anti-inflammatory, regeneration, reactive gliosis, demyelination, estradiol