Krarup Christian, Archibald Simon J, Madison Roger D
Department of Clinical Neurophysiology, National University Hospital (Rigshospitalet), Copenhagen, Denmark.
Ann Neurol. 2002 Jan;51(1):69-81. doi: 10.1002/ana.10054.
Regeneration in the peripheral nervous system is often incomplete though it is uncertain which factors, such as the type and extent of the injury or the method or timing of repair, determine the degree of functional recovery. Serial electrophysiological techniques were used to follow recovery from median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time to earliest muscle reinnervation) on the final recovery of the outcome measures. Nerve gap distance and the repair type, individually and concertedly, strongly influenced the time to earliest muscle reinnervation, and only time to reinnervation was significant when all three variables were included as outcome predictors. Thus, nerve gap distance and repair type exert their influence through time to muscle reinnervation. These findings emphasize that factors that control early axonal outgrowth influence the final level of recovery attained years later. They also highlight that a time window exists within which axons must grow through the distal nerve stump in order for recovery after nerve lesions to be optimal. Future work should focus on interventions that may accelerate the growth of axons from the lesion site into the distal nerve stump.
尽管尚不确定诸如损伤的类型和程度、修复方法或时机等哪些因素决定功能恢复的程度，但周围神经系统的再生往往并不完全。我们使用系列电生理技术，对46只非人灵长类动物正中神经损伤后的恢复情况进行了3至4年的跟踪研究，这一时段与人类此类损伤的时间跨度相当。分别用神经移植物或胶原基神经导管修复5毫米、20毫米或50毫米的神经间隙，并跟踪三项电生理结果指标：（1）拇短展肌的复合肌肉动作电位；（2）再支配肌肉中运动单位的数量和大小；（3）指神经的复合感觉动作电位。我们使用一个统计模型来评估三个变量（修复类型、神经间隙距离以及最早肌肉再支配时间）对这些结果指标最终恢复情况的影响。神经间隙距离和修复类型各自及共同对最早肌肉再支配时间有强烈影响，并且当将所有三个变量作为结果预测指标时，只有再支配时间具有显著意义。因此，神经间隙距离和修复类型通过肌肉再支配时间发挥其影响。这些发现强调，控制早期轴突生长的因素会影响多年后最终的恢复水平。它们还突出表明，存在一个时间窗，轴突必须在这个时间窗内穿过远端神经残端，神经损伤后的恢复才能达到最佳效果。未来的工作应聚焦于可能加速轴突从损伤部位向远端神经残端生长的干预措施。
