Stimulation of spinal cord regeneration by stimulator of NGF synthesis

神经生长因子（NGF）是一种促进交感神经元、神经嵴来源的感觉神经元和基底前脑胆碱能神经元存活和细胞代谢的靶源性营养因子。已知外周神经系统中近端和/或远端断神经残端有NGF水平的增加，它们作为退行性变或神经元细胞死亡的反应可以通过系统给予外源性NGF来预防。脑室内给药NGF可预防老年脑胆碱能神经元的萎缩。虽然脊髓损伤导致严重的功能缺损，但NGF在脊髓中的具体功能尚不清楚。为了进一步了解NGF在脊髓退变/再生过程中的具体功能，我们采用脊髓横断模型，测定横断后NGF和NGFmRNA水平的时间变化。由于NGF广泛分布于幼龄成年大鼠脊髓各节段（200 ~ 300 pg/g湿组织），我们建立了10周龄Wistar大鼠脊髓横断模型（T-6）。横断后第2天（2d），横断部位吻侧残端NGF显著升高（p<0.01）。然后，在两个树桩（吻侧和尾侧），NGF水平在4d时显著增加2 ~ 3倍，在6d时显著增加2 ~ 4倍。从4d到8d，两个残端NGF显著增加，从2d到21d，吻侧残端NGF显著增加。在两个树桩处，NGF mRNA的表达在1d时升高，在2d至8d时逐渐降低。儿茶酚类化合物在细胞培养或周围神经系统中是一种促进NGF合成的刺激物，可以刺激两个残肢中NGF和NGFmRNA水平的增加。这些结果提示NGF可能在脊髓再生中起重要作用。

Nerve growth factor (NGF) is a target derived trophic agent which promotes the survival and cellular metabolism of sympathetic neurons, neural crest-derived sensory neurons and basal forebrain cholinergic neurons. It is known that the proximal and/or distal stumps of severed nerve in the peripheral nervous system have an increase in NGF levels, and their responses as degeneration or neuronal cell death can be prevented with systemically administered exogenous NGF. The atrophy of cholinergic neurons in aged brain can be prevented with intraventricular administration of NGF. Although the spinal cord injury results the serious functional deficit, the specific function of NGF in the spinal cord is unknown.With the aim of gaining insight into the specific function of NGF in the spinal cord during degeneration/regeneration, we used the model of spinal cord transection, and determined temporal changes of NGF and NGFmRNA levels after the transection. As NGF displays a broad distribution in each segment (200 to 300 pg/g wet tissue) of spinal cord in young adult rat, we established the model of spinal cord transection (T-6) on 10-week-old Wistar rat. In the beginning at 2 days after transection (2d), NGF displays a significant increase at the rostral stump of transection site (p<0.01). Then, at both (rostral and caudal) stumps, the level of NGF significantly increase 2 to 3-folds at 4d, 2 to 4-folds at 6d. The significant increases of NGF at both stumps are detected from 4d through 8d, and those at the rostral stump are detected from 2d through 21d. At the both stumps, the expression of NGF mRNA increase at 1d,then gradually decrease from 2d though 8d. The increase of NGF and NGFmRNA levels in the both stumps are stimulated by the administration of catechol compound, which is known to be a stimulator of NGF synthesis in cell culture or peripheral nervous system. These results suggest that NGF may play an important role in the regeneration of spinal cord.