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、神经峰源性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，周围神经系统中神经断端的近端和/或远端有NGF水平的增加，系统地应用外源性NGF可以防止它们的变性或神经细胞死亡。脑室注射NGF可预防老年大鼠脑内胆碱能神经元的萎缩。虽然脊髓损伤导致严重的功能缺陷，但NGF在脊髓中的具体功能尚不清楚。为了深入了解NGF在脊髓变性/再生过程中的特定功能，我们采用脊髓横断模型，测定了脊髓横断后NGF和NGFmRNA水平的时间变化。鉴于NGF广泛分布于幼年大鼠脊髓各节段(200~300pg/g湿组织)，我们建立了10周龄Wistar大鼠脊髓横断(T-6)模型。在横断后2天开始，神经生长因子在横断部位的吻侧残端显著增加(p&lt；0.01)。在两个树桩上，NGF水平在4d时显著增加2~3倍，在6d时增加2~4倍。从第4天到第8天，两个树桩的NGF含量显著增加，而在吻部树桩，从第2天到第21天，NGF的含量显著增加。在两个树桩上，NGF mRNA的表达在1d开始增加，然后从2d到8d逐渐降低。在细胞培养或外周神经系统中，邻苯二酚化合物可刺激神经生长因子的合成，从而刺激神经生长因子和神经生长因子基因的表达。提示NGF在脊髓再生中可能起重要作用。

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.