Thomas C K, Erb D E, Grumbles R M, Bunge R P
The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami School of Medicine, Miami 33136, Florida, USA.
J Neurophysiol. 2000 Jul;84(1):591-5. doi: 10.1152/jn.2000.84.1.591.
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.
去神经支配后骨骼肌的快速萎缩严重影响了恢复肌肉功能的努力。我们将胚胎第14 - 15天（E14 - E15）的腹侧脊髓细胞移植到成年Fischer大鼠的胫神经残端，以提供用于重新支配的神经元。我们的目的是从生理上评估腓肠肌内侧的重新支配情况，因为只有当重新支配的肌肉能够收缩、产生足够的力量以引起关节运动并且具有足够的抗疲劳能力以反复缩短时，这种移植策略才会有效。移植后12周，对移植物施加短暂的电刺激可诱导腓肠肌内侧收缩，在12只大鼠中有4只（33%）收缩强度足以产生踝关节运动。在五个小时的间歇性超强刺激过程中，这四块“低阈值”重新支配肌肉和对照肌肉的力量仅逐渐下降，且肌电图电位面积没有降低，这有力地证明了功能性神经肌肉接头和抗疲劳肌肉的存在。切断腓肠肌内侧神经证实这些收缩依赖于神经支配。低阈值重新支配肌肉的无力（为对照力量的8%）与重新支配不完全、肌纤维大小减小、比张力降低和/或存在无功能的神经肌肉接头有关。使用这种新型移植策略实现的肌肉重新支配可能挽救完全去神经支配的肌肉，并在损伤或疾病阻止或延迟周围轴突再生时提供引发肢体运动的潜力。
