Oudega M, Hagg T
Miami Project to Cure Paralysis, University of Miami School of Medicine, Florida 33136, USA.
Exp Neurol. 1996 Aug;140(2):218-29. doi: 10.1006/exnr.1996.0131.
Injured adult mammalian axons are unable to regenerate spontaneously in the central nervous tissue. This study investigated in two adult rat models the effects of nerve growth factor (NGF) on the capacity of central primary sensory axons to regenerate back into the spinal cord. Sensory fibers were conditioned by transection of the peripheral nerve 1 week prior to the experiment and identified by anterograde tracing with cholera toxin B subunit injected in the sciatic nerve. In the first model, a predegenerated autologous peripheral nerve graft was implanted as a bridge for the transected sensory fibers into a resection gap in the dorsal columns at the tenth thoracic (T10) spinal cord segment. Vehicle or vehicle with purified mouse or recombinant human NGF was continuously infused for 2 weeks directly into the dorsal column at T9, 3 mm from the rostral border of the nerve graft. With vehicle infusion many ascending sensory axons had grown across the nerve bridge, but essentially none had grown back into the rostral cord. In sharp contrast, NGF promoted the reentry into the denervated dorsal columns of 51% of the sensory axons that had reached the rostral level of the nerve graft. Twenty-six percent had grown 2 mm into the spinal tissue and 10% had reached the NGF-infusion site at 3 mm from the nerve graft. A few fibers were found circling around, but not beyond, the infusion site, perhaps due to the chemoattractant action of NGF. In a second model, the fourth lumbar (L4) dorsal root was crushed 2 mm from its insertion point into the spinal cord and the dorsal roots L2, L3, L5, and L6 were transected. Vehicle or vehicle with purified mouse NGF was infused for 2 weeks directly into the lumbar spinal cord, 2.5 mm rostral to the transition zone of the crushed L4 root. With vehicle, only 6% of the regenerating fibers at the transition zone had crossed the root-spinal cord barrier, but not farther than 0.5 mm into the spinal tissue. With NGF, 18% of the fibers at the transition zone were found at 0.5 mm, 9% at 1.5 mm, and 5% at 2.5 mm (the infusion site) from the transition zone. The present results demonstrate that NGF can promote the regeneration of adult sensory fibers into the otherwise nonpermissive spinal cord white matter.
成年哺乳动物受损的轴突无法在中枢神经组织中自发再生。本研究在两种成年大鼠模型中，研究了神经生长因子（NGF）对中枢初级感觉轴突再生回脊髓能力的影响。在实验前1周，通过切断外周神经对感觉纤维进行预处理，并通过向坐骨神经注射霍乱毒素B亚基进行顺行示踪来识别。在第一个模型中，将预先变性的自体外周神经移植物作为桥接物，用于横断的感觉纤维接入第十胸椎（T10）脊髓节段背柱的切除间隙。将载体或含有纯化小鼠或重组人NGF的载体连续2周直接注入T9水平的背柱，距离神经移植物头端边界3毫米处。注入载体时，许多上行感觉轴突生长穿过神经桥，但基本上没有轴突生长回头端脊髓。与之形成鲜明对比的是，NGF促进了51%已到达神经移植物头端水平的感觉轴突重新进入去神经支配的背柱。26%的轴突生长进入脊髓组织2毫米，10%的轴突到达距离神经移植物3毫米处的NGF注入部位。发现少数纤维在注入部位周围环绕，但未超过该部位，这可能是由于NGF的化学吸引作用。在第二个模型中，第四腰（L4）背根在距其进入脊髓的插入点2毫米处被挤压，L2、L3、L5和L6背根被横断。将载体或含有纯化小鼠NGF的载体连续2周直接注入腰脊髓，在被挤压的L4神经根过渡区头端2.5毫米处。注入载体时，过渡区只有6%的再生纤维穿过根-脊髓屏障，但进入脊髓组织的距离不超过0.
