Department of Anesthesiology, Changzheng Hospital, The Second Military Medical University, Shanghai, China.
Spinal Cord. 2010 Dec;48(12):850-6. doi: 10.1038/sc.2010.47. Epub 2010 May 11.
To evaluate the role of corticotrophin-releasing hormone (CRH) in facilitating axon outgrowth.
Injured neural tissue is difficult to regenerate; the mechanism has not been fully understood.
A rat model of spinal cord transection injury was developed. Levels of BDNF, CRH and oligodendrocyte glycoprotein (OMgp) in injured spinal cord were monitored dynamically after surgery. Cellular interaction among rat dorsal root ganglia (DRG) cells, oligocondrocytes and microglial cells was observed with a coculture model. The axon outgrowth from DRG cells was examined by confocal microscopy.
After spinal cord transection, levels of BDNF and CRH increased the next day and decreased afterward, whereas OMgp levels increased from day 3. Administration with BDNF suppressed the levels of OMgp in vitro. The results from a coculture model showed that CRH increased microglial cells to release BDNF; BDNF inhibited OMgp levels in oligodendrocytes and enhanced the axon outgrowth from DRG cells.
This study shows that CRH has the ability to facilitate the outgrowth of axon in spinal neurons, which has therapeutic potential in the treatment of spinal cord injury.
评估促肾上腺皮质激素释放激素(CRH)在促进轴突生长中的作用。
受损的神经组织难以再生;其机制尚未完全阐明。
建立大鼠脊髓横断损伤模型。术后动态监测损伤脊髓中 BDNF、CRH 和少突胶质细胞糖蛋白(OMgp)的水平。利用共培养模型观察大鼠背根神经节(DRG)细胞、少突胶质细胞和小胶质细胞之间的细胞相互作用。通过共聚焦显微镜检查 DRG 细胞的轴突生长情况。
脊髓横断后,BDNF 和 CRH 的水平在次日增加,随后降低,而 OMgp 的水平从第 3 天开始增加。BDNF 的给药抑制了体外 OMgp 的水平。共培养模型的结果表明,CRH 增加小胶质细胞释放 BDNF;BDNF 抑制少突胶质细胞中的 OMgp 水平并增强 DRG 细胞的轴突生长。
本研究表明,CRH 具有促进脊髓神经元轴突生长的能力,这在治疗脊髓损伤方面具有潜在的治疗价值。