Pharmacological Analysis of Neurite Re-elongation

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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.