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

Selective CDK inhibitors: promising candidates for future clinical traumatic brain injury trials.
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选择性 CDK 抑制剂:未来临床创伤性脑损伤试验的有希望的候选者。

DOI:
10.4103/1673-5374.141779
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发表时间:
2014-09-01
影响因子:
6.1
通讯作者:
Faden AI
Faden AI
中科院分区:
医学2区
文献类型:
--
作者:
Kabadi SV;Faden AI

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创伤性脑损伤导致继发性损伤,导致神经炎症、神经元丢失和神经功能障碍。其中一个重要的损伤机制是激活细胞周期,导致神经元的凋亡和胶质细胞的激活。非选择性(黄吡哆醇)和选择性(罗索维汀和CR-8)细胞周期蛋白依赖性激酶抑制剂的神经保护作用已在多种实验性脑损伤模型和物种中得到证明。脑创伤后24小时内单次全身给药的细胞周期蛋白依赖性激酶抑制剂可提供强大的神经保护作用--减少神经细胞死亡、神经炎症和神经功能障碍。鉴于它们的有效性和较长的治疗窗口,细胞周期蛋白依赖的激酶抑制剂似乎是临床创伤性脑损伤试验的有希望的候选药物。
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.
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