Byrnes Kimberly R, Stoica Bogdan A, Fricke Stanley, Di Giovanni Simone, Faden Alan I
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
Brain. 2007 Nov;130(Pt 11):2977-92. doi: 10.1093/brain/awm179. Epub 2007 Aug 9.
Spinal cord injury (SCI) causes delayed secondary biochemical alterations that lead to tissue loss and associated neurological dysfunction. Up-regulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. The present study examined the role of cell cycle activation on secondary injury after severe SCI in rat. SCI caused cell cycle protein up-regulation associated with neuronal and oligodendroglial apoptosis, glial scar formation and microglial activation. Treatment with the cell cycle inhibitor flavopiridol reduced cell cycle protein induction and significantly improved functional recovery versus vehicle-treated controls at 21 and 28 days post-injury. Treatment also significantly reduced lesion volume, as measured by MRI and histology, decreased astrocytic reactivity, attenuated neuronal and oligodendroglial apoptosis and reduced the production of factors associated with microglial activation. Thus, flavopiridol treatment improves outcome after SCI by inhibiting cell cycle pathways, resulting in beneficial multifactorial actions on neurons and glia.
脊髓损伤（SCI）会引发延迟性的继发性生化改变，进而导致组织损失及相关的神经功能障碍。脊髓损伤后，神经元和神经胶质细胞中细胞周期蛋白均会上调，这可能促使了这些变化的发生。本研究探究了细胞周期激活在大鼠严重脊髓损伤后继发性损伤中的作用。脊髓损伤导致细胞周期蛋白上调，同时伴有神经元和少突胶质细胞凋亡、胶质瘢痕形成以及小胶质细胞激活。与损伤后21天和28天接受载体治疗的对照组相比，使用细胞周期抑制剂黄酮哌啶醇进行治疗可降低细胞周期蛋白的诱导水平，并显著改善功能恢复情况。通过磁共振成像（MRI）和组织学测量发现，该治疗还显著减小了损伤体积，降低了星形细胞反应性，减轻了神经元和少突胶质细胞凋亡，并减少了与小胶质细胞激活相关的因子产生。因此，黄酮哌啶醇治疗通过抑制细胞周期途径改善了脊髓损伤后的预后，对神经元和神经胶质细胞产生了有益的多因素作用。
