Ruigt G S, Makkink W K, Konings P N
Neuropharmacology Department, NV Organon, Netherlands.
Neurosci Lett. 1996 Jan 12;203(1):9-12. doi: 10.1016/0304-3940(95)12251-6.
A co-culture system of intact rat dorsal root ganglia (DRG) with Schwann cells was used to evaluate the potential neurotrophic activity of SR 57746A. Neuritogenesis from DRG was measured with an image analysis system following exposure to different concentrations of SR 57746A. Neurite outgrowth of intact DRG was increased by SR 57746A and this was more obvious in the presence of co-cultured Schwann cells. The neuroprotective properties of SR 57746A were studied in co-cultures of DRG and Schwann cells, in which neuritogenesis was reduced by the cytostatic drugs cisplatin, vincristine and taxol. It was found that neurite outgrowth from DRG treated with cisplatin (3 micrograms/ml) and 10 microM SR 57746A for 3 days was significantly higher than after treatment with cisplatin alone. Similarly, neuritogenesis from DRG treated with taxol (0.01 microgram/ml) or vincristine (0.5 ng/ml) in combination with 10 microM SR 57746A was significantly increased compared to treatment with taxol or vincristine alone. When intact DRG were incubated in vitro with 3 micrograms/ml cisplatin and without Schwann cells, 10 microM SR 57746A also had a neuroprotective effect. These data suggest that SR 57746A has neuroprotective potential and that this effect does not depend solely on the presence of Schwann cells.
采用完整大鼠背根神经节（DRG）与雪旺细胞的共培养系统来评估SR 57746A的潜在神经营养活性。在暴露于不同浓度的SR 57746A后，使用图像分析系统测量DRG的神经突生成。SR 57746A可增加完整DRG的神经突生长，并且在共培养雪旺细胞的情况下这种作用更明显。在DRG和雪旺细胞的共培养物中研究了SR 57746A的神经保护特性，在该共培养物中，细胞生长抑制剂顺铂、长春新碱和紫杉醇可减少神经突生成。结果发现，用顺铂（3微克/毫升）和10微摩尔SR 57746A处理3天的DRG的神经突生长明显高于单独用顺铂处理后。同样，与单独用紫杉醇或长春新碱处理相比，用紫杉醇（0.01微克/毫升）或长春新碱（0.5纳克/毫升）联合10微摩尔SR 57746A处理的DRG的神经突生成显著增加。当完整DRG在体外与3微克/毫升顺铂一起孵育且没有雪旺细胞时，10微摩尔SR 57746A也具有神经保护作用。这些数据表明，SR 57746A具有神经保护潜力，并且这种作用并不完全依赖于雪旺细胞的存在。
