From the Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine.
Section of Plastic and Reconstructive Surgery, Department of Surgery, University of Michigan.
Plast Reconstr Surg. 2023 Apr 1;151(4):792-803. doi: 10.1097/PRS.0000000000009999. Epub 2022 Dec 6.
Terminal Schwann cells (tSCs), nonmyelinating glial cells at the neuromuscular junction (NMJ), are integral to NMJ development, function, remodeling, and response to injury. It is essential to understand their requirement for NMJ function. In this study, the authors assessed consequences of immune-mediated tSC ablation in adult S100 -GFP mice of both sexes in homeostasis and after nerve injury.
The authors examined NMJ morphology and function in the extensor digitorum longus muscle during homeostasis at post-tSC ablation days 3, 14, and 42 and after peroneal nerve transection and immediate repair at 3 and 6 weeks after nerve injury and tSC ablation (postinjury and ablation).
tSC ablation resulted in significant decreases ( P < 0.05) in tSC numbers per NMJ and end plate fragmentation. NMJ innervation and EDL tetanic force were significantly decreased at post-tSC ablation day 14 ( P < 0.05) and tSCs reestablished their NMJ coverage at post-tSC ablation day 42. After nerve injury, motor end plate fragmentation increased ( P < 0.01) with tSC ablation compared with injured control mice. NMJ reinnervation and extensor digitorum longus tetanic force were significantly reduced ( P < 0.001), even at 6 weeks postinjury and ablation, compared with control mice.
These results add to the understanding that tSCs, with their proregenerative potential, help maintain NMJ integrity in homeostasis and are necessary for NMJ reinnervation after peripheral nerve injury.
Terminal Schwann cells are integral for efficient NMJ recovery after nerve injury. This cell population may provide a novel therapeutic target to improve outcomes for patients with nerve injuries; additional investigation is warranted.
终端雪旺细胞（tSCs）是神经肌肉接头（NMJ）处的非髓鞘胶质细胞，对于 NMJ 的发育、功能、重塑以及对损伤的反应都至关重要。了解它们对 NMJ 功能的需求至关重要。在这项研究中，作者评估了 S100-GFP 雌雄小鼠在稳态和神经损伤后免疫介导的 tSC 消融对 NMJ 的影响。
作者在 tSC 消融后第 3、14 和 42 天以及周围神经横断和即时修复后 3 和 6 周，检查了伸趾长肌 NMJ 的形态和功能。
tSC 消融导致 NMJ 上 tSC 数量和终板碎片显著减少（P < 0.05）。tSC 消融后第 14 天（P < 0.05），NMJ 神经支配和 EDL 强直力显著下降，tSC 在 tSC 消融后第 42 天恢复了对 NMJ 的覆盖。神经损伤后，与未损伤对照小鼠相比，tSC 消融导致运动终板碎片增加（P < 0.01）。NMJ 再神经支配和伸趾长肌强直力显著降低（P < 0.001），即使在损伤和消融后 6 周，与对照小鼠相比也是如此。
这些结果增加了对 tSCs 的理解，即它们具有促再生潜力，有助于维持 NMJ 在稳态下的完整性，并在周围神经损伤后对 NMJ 再神经支配至关重要。
终端雪旺细胞是神经损伤后 NMJ 恢复的关键。该细胞群体可能为改善神经损伤患者的预后提供新的治疗靶点；需要进一步研究。
