Pharmacological Analysis of Neurite Re-elongation

本课题的目的是寻找能促进损伤神经元轴突再伸长和分支的物质，并阐明其药理学机制。在1994年，我们证明了多胺强烈促进神经突再伸长。当精胺，多胺之一，与碱性成纤维细胞生长因子，这已被证明是促进神经突分支共处理，他们促进神经突的再伸长和分支上相同的神经元。这些结果表明，神经突的再克隆和分支是独立调节的。在1995年，我们发现白细胞介素-2（IL-2），而不是IL-6，增强了神经突分支，尽管它们都被证明对完整的（未受损的）神经元发挥神经营养作用。提示IL-2和IL-6对中枢神经元再生有明显的促进作用。根据这些结果，多胺和IL-2现在被确定为用于治疗由诸如中风或脑缺血引起的脑损伤的候选药剂。最近，我们证明，利用海马切片培养技术，GABA拮抗剂印防己毒素产生的癫痫样活动，防止突触形成的海马苔藓纤维通过L-型钙通道激活物理损伤的神经元网络。

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.