中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (1): 7-12.doi: 10.4103/1673-5374.198964

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

脑源性神经营养因子和其小分子模拟物对创伤性脑损伤的治疗潜力

  

  • 收稿日期:2017-01-16 出版日期:2017-01-15 发布日期:2017-01-15

Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury

Mary Wurzelmann, Jennifer Romeika, Dong Sun*   

  1. Department of Neurosurgery, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
  • Received:2017-01-16 Online:2017-01-15 Published:2017-01-15
  • Contact: Dong Sun, M.D., Ph.D., dsun@vcu.edu.

摘要:

 

创伤性脑损伤是世界范围内的主要健康问题。在主要机械损伤后,接续的继发性损伤常常导致进一步的神经组织损失。到目前为止,还没有挽救受损神经组织的治愈方法。目前的治疗策略主要针对继发性损伤,侧重于神经保护和神经再生。神经营养因子脑源性神经营养因子(BDNF)在促进神经元存活、突触可塑性和神经发生方面具有显著效果。最近,模拟BDNF功能的类黄酮7,8-二羟基黄酮(7,8-DHF),一种小TrkB激动剂,其显示出与BDNF相似的作用,可以促进创伤性脑损伤后的神经元存活和再生。与BDNF相比,7,8-DHF具有更长的半衰期和更小的分子体积,能够穿透血脑屏障,这使得其可能作为非侵入性临床应用方法。

 

ORCID: 0000-0002-3837-7319(Dong Sun)

Abstract:

Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood brain-barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.   

Key words: 7,8-dihydroxyflavone, BDNF, tropomyosin related kinase B (TrkB) receptor, traumatic brain injury, neuroregeneration, neuroprotection