Nógrádi A, Vrbová G
Department of Ophthalmology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Eur J Neurosci. 1996 Oct;8(10):2198-203. doi: 10.1111/j.1460-9568.1996.tb00741.x.
Loss of motoneurons results in a decrease in force production by skeletal muscles and paralysis. Although it has been shown that missing motoneurons of rats can be replaced by embryonic homotopic neurons, attempts to guide their axons to their target muscles that have lost their innervation have been unsuccessful. In this study attempts were made to guide axons from grafted embryonic motoneurons to their target via a reimplanted ventral root. Adult hosts that received an embryonic graft prelabelled with 5-bromo-2'-deoxyuridine had their L4 ventral root avulsed and reimplanted into the spinal cord. Three to six months later, neurons that had their axons in the L4 ventral ramus were retrogradely labelled with fast blue and diamidino yellow. In five animals that had received an embryonic graft 116 +/- 16 cells were retrogradely labelled, and of these at least 15% were of graft origin, since they were positive for 5-bromo-2'-deoxyuridine. In five animals that had their L4 ventral root reimplanted but did not receive a graft, only 12 +/- 1.3 cells were retrogradely labelled. However, meaningful functional recovery could be achieved only if the regenerating axons of embryonic motoneurons found in the L4 ventral ramus were able to reverse the loss of force of muscles that had lost their innervation. This study shows that axons of embryonic motoneurons grafted into an adult rat spinal cord, as well as some axons of host origin, can be guided to denervated hindlimb muscles via reimplanted lumbar ventral roots. In normal rats approximately 30 motor axons innervated the extensor digitorum longus and 60 innervated the tibialis anterior via the L4 ventral root. In rats that did not receive a graft only 3.7 +/- 1.2 axons reached the extensor digitorum longus and 3.5 +/- 0.4 reached the tibialis anterior muscle via the implanted L4 ventral root. In animals that had an embryonic graft, 7.6 +/- 0.5 axons innervated the extensor digitorum longus and 8.5 +/- 0.5 reached the tibialis anterior muscle via the implanted root. In rats without a transplant the maximum tetanic tension elicited by stimulating the implanted L4 root was 16 +/- 7 g for the extensor digitorum longus and 53 +/- 36 g for the tibialis anterior muscle, whereas the corresponding muscles in animals that had an embryonic graft developed 82 +/- 16 and 281 +/- 95 g respectively. Thus it appears that the grafted motoneurons contributed to the innervation and functional recovery of the denervated muscles.
运动神经元的缺失会导致骨骼肌力量产生下降并引发瘫痪。尽管已经表明大鼠缺失的运动神经元可被胚胎同源神经元替代，但引导这些神经元的轴突至失去神经支配的目标肌肉的尝试却未成功。在本研究中，尝试通过重新植入的腹根将移植的胚胎运动神经元的轴突引导至其目标。预先用5-溴-2'-脱氧尿苷标记胚胎移植体的成年宿主，其L4腹根被撕脱并重新植入脊髓。三到六个月后，轴突位于L4腹侧支的神经元用快蓝和双脒基黄进行逆行标记。在接受胚胎移植的五只动物中，有116±16个细胞被逆行标记，其中至少15%来源于移植体，因为它们对5-溴-2'-脱氧尿苷呈阳性。在五只L4腹根被重新植入但未接受移植的动物中，仅有12±1.3个细胞被逆行标记。然而，只有当在L4腹侧支中发现的胚胎运动神经元的再生轴突能够逆转失去神经支配的肌肉的力量损失时，才能实现有意义的功能恢复。本研究表明，移植到成年大鼠脊髓中的胚胎运动神经元的轴突以及一些宿主来源的轴突，可以通过重新植入的腰段腹根被引导至失神经的后肢肌肉。在正常大鼠中，约30条运动轴突通过L4腹根支配趾长伸肌，60条支配胫骨前肌。在未接受移植的大鼠中，通过植入的L4腹根仅有3.7±1.2条轴突到达趾长伸肌，3.5±0.4条到达胫骨前肌。在接受胚胎移植的动物中，有7.6±0.5条轴突支配趾长伸肌，8.5±0.5条通过植入的腹根到达胫骨前肌。在未进行移植的大鼠中，刺激植入的L4根所引发的趾长伸肌最大强直张力为16±7 g，胫骨前肌为53±36 g，而在接受胚胎移植的动物中，相应肌肉分别产生了82±16 g和281±95 g的张力。因此，似乎移植的运动神经元对失神经肌肉的神经支配和功能恢复有贡献。
