Malgrange B, Delrée P, Rigo J M, Baron H, Moonen G
Department of Human Physiology and Pathophysiology, University of Liège, Belgium.
J Neurosci Methods. 1994 Jul;53(1):111-22. doi: 10.1016/0165-0270(94)90151-1.
Peripheral neuropathies are a common side effect of chemotherapeutic agents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociated cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents, with the establishment of dose-response curves and the calculation of IC50; (ii) quantification of neurotrophic effects; and (iii) demonstration of neuroprotection by trophic factors. In particular, we show that nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) stimulate in vitro neuritic regeneration by adult rat DRG neurons, while brain-derived neurotrophic factor and neurotrophin-3 lack such effects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically decreases the neurotoxic effect of vincristine and cisplatin.
周围神经病变是化疗药物的常见副作用,尤其是诸如紫杉醇、顺铂或长春花生物碱(长春新碱、长春碱、长春地辛)等抗肿瘤药物。利用成年大鼠背根神经节(DRG)神经元的解离培养物以及神经丝免疫染色后的视频图像分析,我们设计了一种系统,该系统能够:(i)快速筛选潜在的神经毒性药物,建立剂量反应曲线并计算IC50;(ii)量化神经营养作用;(iii)证明营养因子的神经保护作用。特别地,我们发现神经生长因子(NGF)和碱性成纤维细胞生长因子(bFGF)可刺激成年大鼠DRG神经元的体外神经突再生,而脑源性神经营养因子和神经营养素-3则缺乏这种作用。此外,NGF或bFGF预处理24小时可显著降低长春新碱和顺铂的神经毒性作用。