Horvat J C, Affane-Boulaid F, Baillet-Derbin C, Davarpanah Y, Destombes J, Duchossoy Y, Emery E, Kassar-Duchossoy L, Mira J C, Moissonnier P, Pécot-Dechavassine M, Reviron T, Rhrich-Haddout F, Tadié M, Ye J H
Laboratoire de Neurobiologie, URA CNRS 1448, Université Paris V-René-Descartes.
C R Seances Soc Biol Fil. 1997;191(5-6):717-29.
In an attempt at repairing the injured spinal cord of adult mammals (rat, dog and marmoset) and its damaged muscular connections, we are currently using: 1) peripheral nerve autografts (PNG), containing Schwann cells, to trigger and direct axonal regrowth from host and/or transplanted motoneurons towards denervated muscular targets; 2) foetal spinal cord transplants to replace lost neurons. In adult rats and marmosets, a PNG bridge was used to joint the injured cervical spinal cord to a denervated skeletal muscle (longissimus atlantis [rat] or biceps brachii [rat and marmoset]). The spinal lesion was obtained by the implantation procedure of the PNG. After a post-operative delay ranging from 2 to 22 months, the animals were checked electrophysiologically for functional muscular reconnection and processed for a morphological study including retrograde axonal tracing (HRP, Fast Blue, True Blue), histochemistry (AChE, ATPase), immunocytochemistry (ChAT) and EM. It was thus demonstrated that host motoneurons of the cervical enlargement could extend axons all the way through the PNG bridge as: a) in anaesthetized animals, contraction of the reconnected muscle could be obtained by electrical stimulation of the grafted nerve; b) the retrograde axonal tracing studies indicated that a great number of host cervical neurons extended axons into the PNG bridge up to the muscle; c) many of them were assumed to be motoneurons (double labelling with True Blue and an antibody against ChAT); and even alpha-motoneurons (type C axosomatic synapses in HRP labelled neurons seen in EM in the rat); d) numerous ectopic endplates were seen around the intramuscular tip of the PNG. In larger (cavitation) spinal lesions (rat), foetal motoneurons contained in E14 spinal cord transplants could similarly grow axons through PNG bridges up to the reconnected muscle. Taking all these data into account, it can be concluded that neural transplants are interesting tools for evaluating both the plasticity and the repair capacities of the mammalian spinal cord and of its muscular connections.
为了尝试修复成年哺乳动物（大鼠、狗和狨猴）受损的脊髓及其受损的肌肉连接，我们目前正在使用：1）含有施万细胞的周围神经自体移植（PNG），以触发并引导宿主和/或移植的运动神经元的轴突再生，使其朝向失神经支配的肌肉靶标生长；2）胎儿脊髓移植以替代丢失的神经元。在成年大鼠和狨猴中，使用PNG桥将受伤的颈脊髓与失神经支配的骨骼肌（大鼠的寰最长肌或大鼠和狨猴的肱二头肌）相连。通过PNG的植入程序造成脊髓损伤。术后延迟2至22个月后，对动物进行电生理检查以检测功能性肌肉重新连接情况，并进行形态学研究，包括逆行轴突追踪（辣根过氧化物酶、快蓝、真蓝）、组织化学（乙酰胆碱酯酶、三磷酸腺苷酶）、免疫细胞化学（胆碱乙酰转移酶）和电子显微镜检查。结果表明，颈膨大的宿主运动神经元可以通过PNG桥全程延伸轴突，具体表现为：a）在麻醉动物中，通过电刺激移植神经可使重新连接的肌肉收缩；b）逆行轴突追踪研究表明，大量宿主颈神经元将轴突延伸至PNG桥直至肌肉；c）其中许多被认为是运动神经元（真蓝与抗胆碱乙酰转移酶抗体双重标记）；甚至是α运动神经元（在大鼠电子显微镜下可见辣根过氧化物酶标记神经元中的C型轴体突触）；d）在PNG肌肉内尖端周围可见大量异位终板。在较大（有空洞形成）的脊髓损伤（大鼠）中，E14脊髓移植中含有的胎儿运动神经元同样可以通过PNG桥将轴突生长至重新连接的肌肉。综合所有这些数据，可以得出结论，神经移植是评估哺乳动物脊髓及其肌肉连接的可塑性和修复能力的有趣工具。
