Pharmacological Analysis of Neurite Re-elongation

我们项目的目的是寻找促进受损神经元中轴突再延长和分支的物质，并阐明这种活性的药理学机制。1994年，我们证明了多胺强烈地促进了轴突的再延长。当多胺之一的精胺与碱性成纤维细胞生长因子(已被证明促进轴突分支)共同处理时，它们既促进了轴突的再延长，又促进了同一神经元上的分支。这些结果表明，轴突的再克隆和分支是独立调节的。1995年，我们发现IL-2(IL-2)而不是IL-6促进了轴突的分支，尽管两者都被证明对完整的(未损伤的)神经元起到神经营养作用。提示IL-2和IL-6对中枢神经元再生有明显影响。根据这些结果，多胺和IL-2现在被确定为治疗中风或脑缺血等引起的脑损伤的候选药物。最近，我们利用海马片培养技术证明，GABA拮抗剂印防己毒素产生的癫痫样活动通过激活生理受损神经元网络中的L型钙通道来阻止海马苔藓纤维突触的形成。

The object of our project was to search for substances which promote neurite re-elongation and branching in the lesioned neurons and to clarify the pharmacological mechanisms for such activity. In 1994, we demonstrated that polyamines strongly promoted neurite re-elongation. When spermine, one of the polyamines, was cotreated with basic fibroblast growth factor, which had been shown to promote neurite branching, they promoted both neurite re-elongation and branching on the same neurons. These results indicated that neurite re-clongation and branching are regulated independently. In 1995, we found that interleukin-2 (IL-2), but not IL-6, enhanced the neurite branching, although both of them had been shown to exert neurotrophic action on intact (undamaged) neurons. These results suggest that IL-2 and Il-6 has distinct effect on neuronal regeneration in central neurons. From these results, polyamines and IL-2 are now established for candidate agents for the treatment of brain lesions induced by such as stroke or cerebral ischemia. More recently, we demonstrated, utilizing hippocampal slice culture technique, that epileptiform activity produced by GABA antagonist picrotoxin prevents synapse formation of hippocampal mossy fibers via L-type calcium channel activation in physically lesioned neuronal network.