Chaker Sara C, Yan Ling, Sahoo Jugal Kishore, Acikel Cengiz H, Manzanera Esteve Isaac V, Kaplan David L, Levin Michael, Gorantla Vijay S, Thayer Wesley P, Karagoz Huseyin
Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN.
Department of Biomedical Engineering, Tufts University, Medford, MA.
J Hand Surg Glob Online. 2025 Aug 26;7(6):100811. doi: 10.1016/j.jhsg.2025.100811. eCollection 2025 Nov.
Limitations remain in peripheral nerve injury treatments. Previous studies suggest that serotonergic signaling promotes nerve regeneration by facilitating reinnervation and modulating neuronal guidance. This study aimed to evaluate the potential of serotonergic peripheral neuroregeneration using Zolmitriptan, a serotonin receptor agonist.
A total of 24 female Sprague-Dawley rats were divided into four nerve injury cohorts. Sciatic nerve transection and primary repair were performed in two groups, whereas a 1-cm nerve defect was created and repaired with the same nerve segment as an autograft in the other two groups. One primary repair group and one nerve graft group received 1 mL of Zolmitriptan directly to the nerve via sonicated silk protein gels. Control groups received gels without Zolmitriptan. At postoperative 8 weeks, the sciatic nerves were collected for histological analysis. Ex vivo diffusion tensor magnetic resonance imaging was also used to assess axonal regeneration.
The primary repair cohort treated with Zolmitriptan demonstrated robust regeneration, whereas the control cohort showed poorer regeneration. There was no statistical difference in regeneration between the treated and control autograft groups. When evaluating the regeneration rates of the primary repair groups, 80% of the axons successfully extended to the distal end in the Zolmitriptan group, compared with 57% in the control group. In the autograft groups, these rates were 65% for Zolmitriptan and 42% for the control. Electron microscopy supported the axonal counting results.
This pilot study suggests that Zolmitriptan may enhance peripheral nerve regeneration following transection injuries, warranting further investigation for clinical translation.
This study presents promising results regarding the potential of serotonin agonists to aid in peripheral nerve recovery. Additional investigation into these findings could inform new treatment strategies for peripheral nerve injuries.
周围神经损伤治疗仍存在局限性。先前的研究表明，血清素能信号通过促进神经再支配和调节神经元导向来促进神经再生。本研究旨在评估使用血清素受体激动剂佐米曲普坦促进周围神经再生的潜力。
将24只雌性Sprague-Dawley大鼠分为四个神经损伤组。两组进行坐骨神经横断和一期修复，另外两组制造1厘米的神经缺损并用自体神经移植进行修复。一个一期修复组和一个神经移植组通过超声处理的丝蛋白凝胶直接向神经给予1毫升佐米曲普坦。对照组接受不含佐米曲普坦的凝胶。术后8周，收集坐骨神经进行组织学分析。还使用离体扩散张量磁共振成像评估轴突再生。
接受佐米曲普坦治疗的一期修复组显示出强劲的再生，而对照组的再生较差。治疗组和对照自体移植组之间的再生没有统计学差异。在评估一期修复组的再生率时，佐米曲普坦组80%的轴突成功延伸至远端，而对照组为57%。在自体移植组中，佐米曲普坦组和对照组的这些比率分别为65%和42%。电子显微镜结果支持轴突计数结果。
这项初步研究表明，佐米曲普坦可能增强横断伤后周围神经的再生，值得进一步研究以实现临床转化。
本研究显示了血清素激动剂有助于周围神经恢复的潜力，令人鼓舞。对这些发现的进一步研究可为周围神经损伤的新治疗策略提供依据。
