Houweling D A, Lankhorst A J, Gispen W H, Bär P R, Joosten E A
Department of Neurology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, 3508 GA, The Netherlands.
Exp Neurol. 1998 Sep;153(1):49-59. doi: 10.1006/exnr.1998.6867.
During development, neurotrophic factors play an important role in the guidance and outgrowth of axons. Our working hypothesis is that neurotrophic factors involved in the development of axons of a particular CNS tract are among the most promising candidates for stimulating and directing the regrowth of fibers of this tract in the lesioned adult animal. The neurotrophin NT-3 is known to be involved in the target selection of outgrowing corticospinal tract (CST) fibers. We studied the capacity of locally applied NT-3 to stimulate and direct the regrowth of axons of the CST in the lesioned adult rat spinal cord. We also studied the effect of NT-3 application on the functional recovery of rats after spinal cord injury, using the gridwalk test. NT-3 was applied at the site of the lesion dissolved into rat tail collagen type I. Four weeks after spinal cord injury and collagen implantation, significantly more CST fibers had regrown into the collagen matrix containing NT-3 (22 +/- 6%, mean +/- SEM) than into the control collagen matrix without NT-3 (7 +/- 2%). No CST fibers grew into areas caudal to the collagen implant. Despite the absence of regrowth of corticospinal axons into host tissue caudal to the lesion area, functional recovery was observed in rats with NT-3 containing collagen implants.
在发育过程中，神经营养因子在轴突的导向和生长中发挥重要作用。我们的工作假设是，参与特定中枢神经系统通路轴突发育的神经营养因子是刺激和引导成年动物损伤后该通路纤维再生的最有希望的候选因子。已知神经营养蛋白NT-3参与生长中的皮质脊髓束（CST）纤维的靶标选择。我们研究了局部应用NT-3刺激和引导成年大鼠脊髓损伤后CST轴突再生的能力。我们还使用网格行走试验研究了应用NT-3对脊髓损伤大鼠功能恢复的影响。将溶解于大鼠I型尾胶原中的NT-3应用于损伤部位。脊髓损伤和胶原植入后四周，长入含NT-3的胶原基质的CST纤维（22±6%，平均值±标准误）明显多于长入不含NT-3的对照胶原基质的纤维（7±2%）。没有CST纤维长入胶原植入物尾侧的区域。尽管皮质脊髓轴突没有向损伤区域尾侧的宿主组织再生，但在植入含NT-3胶原的大鼠中观察到了功能恢复。
