中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 779-780.doi: 10.4103/1673-5374.322461

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

神经修复过程中张力延长策略的临床潜力

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Clinical potential of tension-lengthening strategies during nerve repair

Stanley Bazarek, Justin M. Brown, Sameer B. Shah*   

  1. Department of Neurosurgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA (Bazarek S, Brown JM)
    Department of Neurosurgery, Brigham & Women’s Hospital/Harvard Medical School, Boston, MA, USA (Bazarek S)
    Departments of Orthopedic Surgery and Bioengineering, University of California-San Diego, La Jolla, CA, USA (Shah SB)
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Sameer B. Shah, PhD, sbshah@ucsd.edu; Justin M. Brown, MD, jmbrown@mgh.harvard.edu.
  • Supported by:
    The present work was supported by Department of Defense/CDMRP Award# W81XWH2010510 (to SBS).

摘要: Neural Regen Res:神经修复中张力的应用
实验室工作和最近的临床病例重新引入了一个废弃的概念,即神经张力可用于通过组织间隙实现直接、无移植物修复,从而改善疗效。前期研究已经进行了大量的修复,利用肢体定位来克服间隙,然后逐渐打开关节,直到完全恢复活动范围。修复策略的一个关键组成部分是保护修复接口。为了避免修复部位的高张力造成的历史问题,可以使用神经管将张力从轴突交叉部位重新分配到修复部位近端和远端更坚固的神经外膜和结构良好的神经外膜内组织。这种方法既增强了修复部位的抗拉强度,又减少了再生轴突在间隙处的复杂作用力。拉伸生长的一个有趣的临床应用是,在与远端受体进行更远端和直接的无移植物吻合之前,预先拉长近端神经残端/供体神经。神经修复或重建的主要障碍是失神经后的神经肌肉变性。有一个关键的窗口约18-24个月恢复神经肌肉连接前,肌肉是不可逆转的损失,由于脂肪和纤维化的替代。神经拉伸和随后的远端修复将使穿过单一界面的轴突供体数量最大化,有可能绕过大片退化的远端残端。这种方法可以加速完整神经干的生长,以桥接一个大的间隙,而不是受到生长锥通过移植间隙再生生长的限制。每天8 mm感觉轴突的实验室拉伸受到保留功能的影响,其速度约为内源性再生速度的8倍。生物力学上,这种拉伸的效果既受变形率(更高的应变速率更具破坏性)的影响,也受变形量的影响(给定的变形可以被更长的神经残端更好地耐受;例如,较低的应变)。
    来自美国马萨诸塞州总医院的Stanley Bazarek团队认为,虽然临床前创新主要针对日益优雅的工程化神经移植物,但近端神经残端预拉伸用于神经修复或重建的潜力巨大。成年大鼠急性坐骨神经横断后,近端横断的神经末梢可以被植入装置拉长,超过远端靶点,允许修复超过10mm的间隙,相当于人类的2-3cm间隙。无论在结构上还是功能上,与金标准自体移植相比,延长后的端到端修复显示出更好的结果。这种方法现在正在更大的动物模型中成功地进行,以评估延长术跨越临床相关间隙的潜力,从而建立神经拉伸作为神经系统重建的有力策略。
事实上,这些方法中的一些已经在临床上得到应用,预示着更广泛地将更复杂的策略整合到临床实践中。有许多迹象表明,这种方法可能是额外有用的。预延长可能对脊髓损伤后的神经转移特别有用。例如,在脊髓损伤后,手部的靶肌肉通常位于损伤部位下方,因此尽管皮质输入丢失,在结构上保留了较低的运动神经元和神经肌肉活力。预拉伸将允许受体靶点在结构上保持受支配,直到供体轴突到达更远的位置,最终延迟吻合。即使接受者失去神经支配,伸展生长的加速特性仍然允许在关键时间内恢复以前无法到达的远端靶点。目前实现新功能一年的等待时间可以减少到几个月,可以修复圆锥或马尾神经损伤后的下肢,或者提供额外的神经移植选择来恢复手部。补充技术,如电刺激或药物增强神经再生和肌肉保存,可能会进一步提高再生的结果。
    文章在《中国神经再生研究(英文版)》杂志2022年  4 月  4  期发表。


https://orcid.org/0000-0001-6613-3904 (Sameer B. Shah)

Abstract: A (very) brief history of tension in nerve repair: Successful nerve repair is achieved by conveying as many axons successfully to their targets as possible. Typically, this is best achieved through a direct end-to-end repair under minimal tension (Millesi, 1986). However, this is not feasible in most cases of trauma, where a segment of tissue damage must be excised and overcome. This has most commonly been addressed with the use of nerve grafts to bridge the gap. Autologous nerve grafts are considered the gold standard, with allograft or synthetic substitutes demonstrating some success over shorter distances. Despite their utility, autologous grafts pose challenges of their own. These include functional deficit in the donor distribution (typically sensory), extended operative duration, additional scarring, and a lack of intrinsic blood supply. They are also a poor anatomical match for the stumps being bridged, both internally (disparate neuronal size and composition) as well as externally (often requiring cabled bundles to approximate the caliber of the nerve being repaired). Finally, unlike end-to-end repairs, autologous grafts also require axons to traverse a second repair interface, where a large proportion of axons are lost across the anatomical discontinuity.