中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (17): 1578-1580.doi: 10.4103/1673-5374.141779

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

选择性细胞周期蛋白依赖性激酶抑制剂:创伤性脑损伤未来临床试验中有希望的候选药物

  

  • 收稿日期:2014-08-18 出版日期:2014-09-16 发布日期:2014-09-16

Selective CDK inhibitors: promising candidates for future clinical traumatic brain injury trials

Shruti V. Kabadi, Alan I. Faden   

  1. Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, USA
  • Received:2014-08-18 Online:2014-09-16 Published:2014-09-16
  • Contact: Alan I. Faden, M.D., Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology, Director, Center for Shock, Trauma & Anesthesiology Research (STAR), University of Maryland School of Medicine, Health Sciences Facility II (HSFII), #S247, 20 Penn Street, Baltimore, MD 21201, USA, afaden@anes.umm.edu.

摘要:

创伤性脑损伤会因为神经炎症,神经元缺失和神经功能障碍引发继发性损伤。其中一中重要的损伤机制就是细胞周期激活可引起神经细胞和神经胶质细胞凋亡的激活。非选择性和选择性细胞周期蛋白依赖性激酶抑制剂的神经保护作用已被应用于多个创伤性脑损伤实验模型的治疗之中。细胞周期蛋白依赖性激酶是一类重要的丝氨酸/苏氨酸蛋白激酶,主要生物学作用是以复合物形式出现启动DNA的复制和诱发细胞的有丝分裂。

Abstract:

Traumatic brain injury induces secondary injury that contributes to neuroinflammation, neuronal loss, and neurological dysfunction. One important injury mechanism is cell cycle activation which causes neuronal apoptosis and glial activation. The neuroprotective effects of both non-selective (Flavopiridol) and selective (Roscovitine and CR-8) cyclin-dependent kinase inhibitors have been shown across multiple experimental traumatic brain injury models and species. Cyclin-dependent kinaseinhibitors, administered as a single systemic dose up to 24 hours after traumatic brain injury, provide strong neuroprotection-reducing neuronal cell death, neuroinflammation and neurological dysfunction. Given their effectiveness and long therapeutic window, cyclin-dependent kinase inhibitors appear to be promising candidates for clinical traumatic brain injury trials.

Key words: cell cycle inhibition, lateral fluid percussion, Roscovitine, CR-8, behavior, microglial activation, neurodegeneration