Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Neurotherapeutics. 2011 Apr;8(2):221-8. doi: 10.1007/s13311-011-0028-2.
Traumatic spinal cord injury (SCI) evokes a complex cascade of events with initial mechanical damage leading to secondary injury processes that contribute to further tissue loss and functional impairment. Growing evidence suggests that the cell cycle is activated following SCI. Up-regulation of cell cycle proteins after injury appears to contribute not only to apoptotic cell death of postmitotic cells, including neurons and oligodendrocytes, but also to post-traumatic gliosis and microglial activation. Inhibition of key cell cycle regulatory pathways reduces injury-induced cell death, as well as microglial and astroglial proliferation both in vitro and in vivo. Treatment with cell cycle inhibitors in rodent SCI models prevents neuronal cell death and reduces inflammation, as well as the surrounding glial scar, resulting in markedly reduced lesion volumes and improved motor recovery. Here we review the effects of SCI on cell cycle pathways, as well as the therapeutic potential and mechanism of action of cell cycle inhibitors for this disorder.
创伤性脊髓损伤 (SCI) 引发了一系列复杂的事件级联反应，最初的机械损伤导致继发性损伤过程，导致进一步的组织损失和功能障碍。越来越多的证据表明，SCI 后细胞周期被激活。损伤后细胞周期蛋白的上调不仅似乎导致有丝分裂后细胞（包括神经元和少突胶质细胞）的凋亡性细胞死亡，而且还导致创伤后神经胶质增生和小胶质细胞激活。抑制关键的细胞周期调控途径可减少损伤诱导的细胞死亡以及体外和体内的小胶质细胞和星形胶质细胞增殖。在 SCI 啮齿动物模型中使用细胞周期抑制剂可防止神经元细胞死亡并减少炎症以及周围的神经胶质瘢痕形成，从而显著减少病变体积并改善运动功能恢复。在这里，我们回顾了 SCI 对细胞周期途径的影响，以及细胞周期抑制剂治疗该疾病的治疗潜力和作用机制。
