中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 846-853.doi: 10.4103/1673-5374.232479

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

促进坐骨神经挤压伤后再生:溶血磷脂酰胆碱联合神经生长因子再生效果的确定

  

  • 收稿日期:2018-02-06 出版日期:2018-05-15 发布日期:2018-05-15
  • 基金资助:

    美国杨百翰大学基金

 Baseline effects of lysophosphatidylcholine and nerve growth factor in a rat model of sciatic nerve regeneration after crush injury

Ryan L. Wood1, Keaton S. Karlinsey2, Austin D. Thompson2, Mark N. Rigby2, Greggory D. Boatright2, William G. Pitt1, Beverly L. Roeder3, Scott C. Steffensen2, 4, Alonzo D. Cook1, 2   

  1. 1 Department of Chemical Engineering, Brigham Young University, Provo, UT, USA;
    2 Neuroscience Center, Brigham Young University, Provo, UT, USA;
    3 Department of Biology, Brigham Young University, Provo, UT, USA;
    4 Department of Psychology, Brigham Young University, Provo, UT, USA
  • Received:2018-02-06 Online:2018-05-15 Published:2018-05-15
  • Contact: Alonzo D. Cook, Ph.D.,cook@byu.edu.
  • Supported by:

    Funding for animal care and supplies was provided by Brigham Young University, the Don B. Olsen Mentorship to RLW, and a Brigham Young University Office of Research and Creative Activities Student Mentored Research Grant to KSK.

摘要:

溶血磷脂酰胆碱可刺激许旺细胞产生神经生长因子(NGF)受体,从而促进损伤周围神经再生。为检验溶血磷脂酰胆碱和神经生长因子单次与多次神经内注射对挤压伤坐骨神经再生的影响。术后立即单次神经内注射1mg/ml 的溶血磷脂酰胆碱或分别于术后7天单次神经内注射160 ng/ml的神经生长因子。多次神经生长因子注射的实验中,大鼠在神经挤压损伤后立即注射10mg/ml (1%wt / vol )溶血磷脂酰胆碱,神经生长因子则以80 ng / ml的浓度被分别于术后5天单次注射,术后5和7天2次注射,术后5,7,9天3次注射。通过步态的监测、电生理(复合肌肉动作电位(CMAP)振幅)和形态学参数(总神经束面积,有髓纤维数,纤维密度,纤维填充和g比值)的检测,观察神经再生情况。溶血磷脂酰胆碱和神经生长因子单次与多次神经内注射未对电生理参数有明显影响,对形态学参数的影响仅在第3周时观察得到。单次注射溶血磷脂酰胆碱和神经生长因子或者在伤后3次注射神经生长因子不会在第1-6周改变坐骨神经愈合率。实验结果表明,溶血磷脂酰胆碱和神经生长因子单次或多次注射的组合并不影响坐骨神经挤压伤后的总体恢复情况,这对于确定神经生长因子和溶血磷脂酰胆碱注射促进周围神经再生的最小剂量有重要意义。

orcid:0000-0002-6032-4926(Alonzo D. Cook)

关键词: 溶血磷脂酰胆碱, 神经营养因子, 生长因子, 坐骨神经, 周围神经, 再生

Abstract:

Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins,upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor (NGF) is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine (LPC) has been shown to stimulate NGF receptors (NGFR). This study tested the administration of a single intraneural injection of LPC (1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections) at day 0 and one (day 7), two (days 5 and 7), or three (days 5, 7, and 9) injections of NGF (160 ng/mL for single injections and 80 ng/mL for multiple injections) to determine baseline effects on crush ed sciatic nerves in rats. The rats were randomly divided into four groups: control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters: compound muscle action potential (CMAP) amplitudes; and morphological parameters: total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush-LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.

Key words: lysophosphatidylcholine, neurotrophic factor, growth factor, sciatic nerve, crush, peripheral nerve, regeneration