Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
J Neurotrauma. 2011 Mar;28(3):441-50. doi: 10.1089/neu.2010.1473. Epub 2011 Jan 9.
Adult neurogenesis occurs in the subgranular zone of the hippocampal dentate gyrus, and can be modulated by physiological and pathological events. We examined the effect of vascular endothelial growth factor (VEGF), and the correlation between VEGF and the Raf/MEK/ERK cascade in neurogenesis after traumatic brain injury (TBI). The expression of VEGF and the phosphorylation level of Raf/MEK/ERK were analyzed by Western blot, and TBI-induced neurogenesis was determined by immunofluorescence labeling and confocal microscopic detection. Hippocampal VEGF began to increase after 12 h, and reached a peak at day 7. Along with the upregulation of VEGF, neurogenesis in the hippocampus also increased. Administration of the VEGF antisense oligodeoxynucleotide, or the VEGF receptor-2 antagonist SU1498 (10 μg, ICV), attenuated the phosphorylation of the MAPK cascade proteins and caused a decrease in neurogenesis in the hippocampus. Similarly, administration of the ERK inhibitor PD98059 (500 ng, ICV) also exhibited a suppressive effect on neurogenesis. Our results indicate that VEGF plays an important role in neurogenesis after TBI, and that the process involves VEGF receptor-2 and the Raf/MEK/ERK cascade.
成人神经发生发生在海马齿状回的颗粒下区，并且可以被生理和病理事件所调节。我们研究了血管内皮生长因子（VEGF），以及 VEGF 与创伤性脑损伤（TBI）后神经发生中的 Raf/MEK/ERK 级联之间的相关性。通过 Western blot 分析 VEGF 的表达和 Raf/MEK/ERK 的磷酸化水平，并通过免疫荧光标记和共聚焦显微镜检测来确定 TBI 诱导的神经发生。海马 VEGF 在 12 小时后开始增加，并在第 7 天达到高峰。随着 VEGF 的上调，海马中的神经发生也增加。给予 VEGF 反义寡脱氧核苷酸或 VEGF 受体-2 拮抗剂 SU1498（10μg，ICV），可减弱 MAPK 级联蛋白的磷酸化，并导致海马中的神经发生减少。同样，给予 ERK 抑制剂 PD98059（500ng，ICV）也对神经发生表现出抑制作用。我们的结果表明，VEGF 在 TBI 后神经发生中起重要作用，并且该过程涉及 VEGF 受体-2 和 Raf/MEK/ERK 级联。
