Development of compounds to stimulate peripheral nerve regeneration viainduction of nerve growth factor synthesis.

点击翻译按钮获取中文摘要

Nerve growth factor (NGF) is a protein that stimulates differentiation and maintains survival of sympathetic nerirons and some sensory neurons in peripheral nervous system. Recent works suggest important roles of NGF during peripheral nerve regeneration. This presents a possibility that NGF may be useful for a therapeutic or a promoting agent for nerve injury. We have already found that some kinds of catechol compounds can stimulate NGF synthesis in vitro. In this research, we aimed to evaluate the compounds with NGF synthesis stimulatory activity as stimulators of NGF synthesis in vivo. For this purpose, we screened various compounds and obtain a series of compounds, alkylcatechols, with potent stimulatory activity of NGF synthesis in vitro. Intraperitoneal administration of one of the alkylcatechols induced an increase in NGF protein and NGF mRNA in the adult rat heart and submaxillary gland. The increase in NGF protein was successively translocated from the sciatic nerve to sensory or sympathetic ganglia. Repetitive administration of an analogue of alkylcatechol caused significant elevations of substance P level in sensory ganglia and tyrosine hydroxylase activity in superior cervical ganglia of infant rats. These observations indicate that alkylcatechols can stimulate NGF synthesis in vivo and that the induced NGF has physiological effects on peripheral neurons. Therefore, we tested one of the alkylcatechols whether it can stimulate peripheral nerve regeneration. Daily injection of methylcatechol for 2 weeks increased the numbers of both myelinated and unmyelinated axons that grew across an 8mm gap after entubational repair of sectioned rat sciatic nerve.