Embryonic cord transplants in peripheral nerve restore skeletal muscle function.

Embryonic cord transplants in peripheral nerve restore skeletal muscle function.
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周围神经的胚胎索移植可恢复骨骼肌功能。

DOI:
10.1152/jn.2000.84.1.591
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发表时间:
2000
影响因子:
2.5
通讯作者:
Bunge,RP
Bunge,RP
中科院分区:
医学3区
文献类型:
--
作者:
Thomas,CK;Erb,DE;Grumbles,RM;Bunge,RP

文献摘要

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去神经支配后骨骼肌的迅速萎缩严重损害了恢复肌肉功能的努力。我们将胚胎第 14-15 天 (E14-E15) 腹侧脊髓细胞移植到成年 Fischer 大鼠胫神经残端中,为神经再支配提供神经元。我们的目的是从生理学角度评估内侧腓肠肌神经支配,因为这种移植策略只有在神经支配的肌肉收缩、产生足够的力来诱导关节运动、并且具有足够的抗疲劳能力以反复缩短的情况下才会有效。移植后 12 周,对移植物施加短暂的电刺激,引起腓肠肌内侧收缩,12 只大鼠中有 4 只 (33%) 的收缩强度足以产生踝关节运动。这四块“低阈值”重新神经支配的肌肉和控制肌肉的力量在五个小时的间歇性超最大刺激期间仅逐渐下降,并且肌电图电位区域没有下降,这是功能性神经肌肉接头和抗疲劳肌肉的有力证据。腓肠肌内侧神经的切片证实这些收缩是神经支配依赖性的。低阈值神经支配肌肉无力(8% 控制力)与神经支配不完全、肌纤维尺寸减小、特定张力和/或非功能性神经肌肉接头的存在有关。使用这种新颖的移植策略实现的肌肉神经支配可以挽救完全去神经支配的肌肉,并且可以在损伤或疾病阻止或延迟外周轴突再生时提供激发肢体运动的潜力。
The rapid atrophy of skeletal muscle after denervation severely compromises efforts to restore muscle function. We have transplanted embryonic day 14–15 (E14–E15) ventral spinal cord cells into adult Fischer rat tibial nerve stump to provide neurons for reinnervation. Our aim was to evaluate medial gastrocnemius reinnervation physiologically because this transplant strategy will only be effective if the reinnervated muscle contracts, generates sufficient force to induce joint movement, and is fatigue resistant enough to shorten repeatedly. Twelve weeks posttransplantation, brief duration electrical stimuli applied to the transplants induced medial gastrocnemius contractions that were strong enough to produce ankle movement in 4 of 12 rats (33%). The force of these four “low-threshold” reinnervated muscles and control muscles declined only gradually during five hours of intermittent, supramaximal stimulation and without depression of EMG potential area, which is strong evidence of functional neuromuscular junctions and fatigue resistant muscles. Sectioning of the medial gastrocnemius nerves confirmed that these contractions were innervation dependent. Weakness in low-threshold reinnervated muscles (8% control force) related to incomplete reinnervation, reductions in muscle fiber size, specific tension, and/or the presence of nonfunctional neuromuscular junctions. Muscle reinnervation achieved using this novel transplantation strategy may salvage completely denervated muscle and may provide the potential to evoke limb movement when injury or disease precludes or delays peripheral axon regeneration.