Wood Ryan L, Karlinsey Keaton S, Thompson Austin D, Rigby Mark N, Boatright Greggory D, Pitt William G, Roeder Beverly L, Steffensen Scott C, Cook Alonzo D
Department of Chemical Engineering, Brigham Young University, Provo, UT, USA.
Neuroscience Center, Brigham Young University, Provo, UT, USA.
Neural Regen Res. 2018 May;13(5):846-853. doi: 10.4103/1673-5374.232479.
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 crushed 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.
施万细胞在帮助修复受损神经方面发挥着重要作用。它们有助于清除碎片、产生神经营养因子、上调神经营养因子受体，并形成许旺氏带以引导愈合中的神经。但神经并不总是能产生足够的神经营养因子和神经营养因子受体来自我修复。神经生长因子（NGF）是促进神经愈合的一种重要神经营养因子，并且已表明溶血磷脂酰胆碱（LPC）可刺激NGF受体（NGFR）。本研究测试了在第0天进行单次神经内注射LPC（单次LPC注射为1mg/mL，多次LPC注射为10mg/mL），以及在第1天（第7天）、第2天（第5天和第7天）或第3天（第5天、第7天和第9天）注射NGF（单次注射为160ng/mL，多次注射为80ng/mL）对大鼠坐骨神经挤压伤的基线影响。大鼠被随机分为四组：对照组、挤压伤组、挤压伤-NGF组和挤压伤-LPC-NGF组。通过监测步态每周测量神经愈合情况；电生理参数：复合肌肉动作电位（CMAP）幅度；以及形态学参数：在第3周和第6周时的总束面积、有髓纤维计数、纤维密度、纤维排列和平均g比值。挤压伤组、挤压伤-NGF组和挤压伤-LPC-NGF组在所有六周的电生理参数上与对照组相比均有统计学差异，但在形态学参数上仅在第3周时与对照组不同。在研究过程中，挤压伤组、挤压伤-NGF组和挤压伤-LPC-NGF组之间没有差异。在损伤后第1周-第6周期间，相隔一周单次注射LPC和NGF或在损伤后第5天、第7天和第9天多次注射NGF均未改变坐骨神经的愈合速度。这些发现对于确定NGF和LPC注射的基线影响很重要，这是确定NGF再生周围神经的最小剂量方案这一更大努力的一部分。
