Sun Dong, Bullock M Ross, McGinn Melissa J, Zhou Zhengwen, Altememi Nabil, Hagood Sarah, Hamm Robert, Colello Raymond J
Department of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
Exp Neurol. 2009 Mar;216(1):56-65. doi: 10.1016/j.expneurol.2008.11.011. Epub 2008 Nov 27.
Stem/progenitor cells reside throughout the adult CNS and are actively dividing in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. This neurogenic capacity of the SVZ and DG is enhanced following traumatic brain injury (TBI) suggesting that the adult brain has the inherent potential to restore populations lost to injury. This raises the possibility of developing strategies aimed at harnessing the neurogenic capacity of these regions to repair the damaged brain. One strategy is to enhance neurogenesis with mitogenic factors. As basic fibroblast growth factor (bFGF) is a potent stem cell mitogen, we set out to determine if an intraventricular administration of bFGF following TBI could affect the levels of injury-induced neurogenesis in the SVZ and DG, and the degree to which this is associated with cognitive recovery. Specifically, adult rats received a bFGF intraventricular infusion for 7 days immediately following TBI. BrdU was administered to animals daily at 2-7 days post-injury to label cell proliferation. At 1 or 4 weeks post-injury, brain sections were immunostained for BrdU and neuronal or astrocytic markers. We found that injured animals infused with bFGF exhibited significantly enhanced cell proliferation in the SVZ and the DG at 1 week post-TBI as compared to vehicle-infused animals. Moreover, following bFGF infusion, a greater number of the newly generated cells survived to 4 weeks post-injury, with the majority being neurons. Additionally, animals infused with bFGF showed significant cognitive improvement. Collectively, the current findings suggest that bFGF-enhanced neurogenesis contributes to cognitive recovery following TBI.
干细胞/祖细胞存在于整个成年中枢神经系统中，并在脑室下区（SVZ）和海马齿状回（DG）中活跃分裂。创伤性脑损伤（TBI）后，SVZ和DG的这种神经发生能力增强，这表明成年大脑具有恢复因损伤而丧失的细胞群的内在潜力。这增加了开发旨在利用这些区域的神经发生能力来修复受损大脑的策略的可能性。一种策略是用促有丝分裂因子增强神经发生。由于碱性成纤维细胞生长因子（bFGF）是一种有效的干细胞有丝分裂原，我们着手确定TBI后经脑室给予bFGF是否会影响SVZ和DG中损伤诱导的神经发生水平，以及这与认知恢复的相关程度。具体而言，成年大鼠在TBI后立即接受7天的脑室bFGF输注。在损伤后2 - 7天每天给动物注射BrdU以标记细胞增殖。在损伤后1周或4周，对脑切片进行BrdU以及神经元或星形胶质细胞标志物的免疫染色。我们发现，与输注载体的动物相比，输注bFGF的受伤动物在TBI后1周时SVZ和DG中的细胞增殖显著增强。此外，在输注bFGF后，更多新生成的细胞存活至损伤后4周，其中大多数是神经元。此外，输注bFGF的动物显示出显著的认知改善。总的来说，目前的研究结果表明，bFGF增强的神经发生有助于TBI后的认知恢复。
