Oudega M, Varon S, Hagg T
Department of Biology, University of California at San Diego, La Jolla 92093-0601.
Exp Neurol. 1994 Oct;129(2):194-206. doi: 10.1006/exnr.1994.1161.
The effect of intraspinally implanted predegenerated peripheral nerve grafts and/or conditioning lesions on the regenerative capacity of central ascending sensory axons was investigated in the adult rat. Regenerating sensory fibers were analyzed after their transganglionic labeling with cholera toxin B subunit, usually 1 month after implantation. A conditioning lesion (transection of the tibial and peroneal nerve) caused a fivefold increase in the number of sensory fibers within the fresh graft when applied on the day of grafting and a sevenfold increase when applied 1 week before. In the latter case, a small portion of the fibers (10%) had reached the rostral end of the nerve graft. In the absence of a conditioning lesion, the number of fibers regenerating into a predegenerated nerve graft (collected from the distal part of the peroneal nerve that had been axotomized 1 week earlier) was similar to that found in a fresh graft. However, predegenerated grafts received three and five times more fibers than a fresh graft when conditioning lesions were applied on or 1 week before the day of grafting. With the combination of a predegenerated graft and a 1-week conditioning, most (> 90%) of the regenerating fibers had reached the rostral graft-host border. In animals with a fresh graft, a portion of the axotomized fibers formed terminal club-like structures. Much fewer fibers displayed such clubs in animals with a predegenerated graft or a conditioning lesion, suggesting a preventive action of either treatment. A time-course study with the combined treatments showed that regenerating sensory fibers had already entered the graft after 3 days. Between 1 and 2 weeks, a maximum number of fibers had reached the rostral end of the nerve graft. However, after 2 months, the number of fibers was decreased, i.e., the initial advantage of predegeneration had diminished. The current results demonstrate the necessity of a conditioning lesion for successful regeneration of central sensory fibers, possibly resulting from an earlier induction of the neuronal growth response which allows the axon to enter the graft before the formation of a graft-host barrier. The predegeneration of the nerve graft augments the growth response of the axotomized central sensory fibers, probably by providing a more supportive terrain and/or enhancement of the neuronal response. The presence of a large number of fibers at the rostral graft-host border now provides the opportunity to investigate the effects of neurotrophic factors on the regenerative capacity of the ascending rat sensory fibers into the denervated spinal cord in vivo.
在成年大鼠中研究了脊髓内植入预先变性的周围神经移植物和/或预处理损伤对中枢上行感觉轴突再生能力的影响。在用霍乱毒素B亚基进行跨神经节标记后分析再生的感觉纤维，通常在植入后1个月进行。预处理损伤（切断胫神经和腓总神经）在移植当天施加时，新鲜移植物内的感觉纤维数量增加了五倍，在移植前1周施加时增加了七倍。在后一种情况下，一小部分纤维（10%）到达了神经移植物的头端。在没有预处理损伤的情况下，再生进入预先变性的神经移植物（从1周前已进行轴突切断的腓总神经远端收集）的纤维数量与新鲜移植物中的相似。然而，当在移植当天或移植前1周施加预处理损伤时，预先变性的移植物比新鲜移植物接收的纤维多三到五倍。通过预先变性的移植物和1周预处理的组合，大多数（>90%）再生纤维到达了移植物与宿主的头端边界。在有新鲜移植物的动物中，一部分轴突切断的纤维形成了终末棒状结构。在有预先变性的移植物或预处理损伤的动物中，显示这种棒状结构的纤维要少得多，这表明两种处理都有预防作用。联合处理的时间进程研究表明，再生的感觉纤维在3天后已经进入移植物。在1至2周之间，最多数量的纤维到达了神经移植物的头端。然而，2个月后，纤维数量减少，即预先变性的初始优势减弱。目前的结果表明预处理损伤对于中枢感觉纤维成功再生的必要性，这可能是由于神经元生长反应的早期诱导，使得轴突在移植物与宿主屏障形成之前进入移植物。神经移植物的预先变性增强了轴突切断的中枢感觉纤维的生长反应，可能是通过提供更有利的环境和/或增强神经元反应。现在移植物与宿主头端边界处存在大量纤维，为研究神经营养因子对大鼠上行感觉纤维向去神经脊髓体内再生能力的影响提供了机会。
