Pretreatment of nerve grafts with resveratrol improves axonal regeneration following replantation surgery for nerve root avulsion injury in rats.
Pretreatment of nerve grafts with resveratrol improves axonal regeneration following replantation surgery for nerve root avulsion injury in rats.
复制标题
DOI：
10.3233/rnn-180844
复制
发表时间：
2018-09
影响因子：
2.8
通讯作者：
Hiroki Oda;S. Ohta;R. Ikeguchi;T. Noguchi;Yukitoshi Kaizawa;Hirofumi Yurie;Hisataka Takeuchi;S. Mitsuzawa;S. Matsuda
中科院分区：
文献类型：
--
作者：
Hiroki Oda;S. Ohta;R. Ikeguchi;T. Noguchi;Yukitoshi Kaizawa;Hirofumi Yurie;Hisataka Takeuchi;S. Mitsuzawa;S. Matsuda
背景技术撕脱神经根再植术已被提议用于治疗严重的臂丛神经损伤数十年。但由于技术复杂、功能改进有限，实际应用仍有待实现。目的 在本研究中，我们在神经根撕脱大鼠模型中研究白藜芦醇预处理对用于再植手术的自体神经移植物的影响。方法 使用外植体培养技术进行白藜芦醇预处理。进行了两次外科手术。在第一次手术中，对 Sprague-Dawley 大鼠进行左 C6 神经根撕脱，并收获神经用于自体移植。将收获的移植物进行外植体培养1周。第一次手术后 1 周，进行第二次手术，使用外植体培养的神经移植物重新种植 C6 神经根。第二次手术后 8 周进行组织学和免疫组织化学分析。我们首先比较了外植体培养的神经移植物和新鲜神经移植物之间的结果，然后我们比较了用和没有白藜芦醇预处理的外植体培养的神经移植物之间的结果。在体外研究了使用或不使用白藜芦醇的外植体培养 1 周后在神经移植物内引起的变化。结果 外植体培养 1 周和新鲜神经移植物的结果没有显着差异。在外植体培养基中添加白藜芦醇导致再生轴突的数量和髓鞘厚度以及 C6 脊髓节段中再生运动神经元的数量显着增加。体外分析显示，用白藜芦醇预处理的神经移植物表现出胶质细胞源性神经营养因子（GDNF）表达和去分化雪旺细胞数量显着增加。结论 白藜芦醇可促进神经根撕脱伤再植术后轴突再生；然而，还需要进一步的研究来验证人类的这些发现。
BACKGROUND Replantation of the avulsed nerve root has been proposed for the treatment of severe brachial plexus injury for several decades. However, due to the complexity of the technique and limited functional improvement, practical applications are yet to be implemented. OBJECTIVE In the present study, we investigated the effect of pretreatment with resveratrol on nerve autografts used for replantation surgery in a rat model of nerve root avulsion. METHODS Resveratrol pretreatment was performed using an explant culture technique. Two surgical procedures were performed. During the first surgery, Sprague-Dawley rats were subjected to left C6 nerve root avulsion, and nerves were harvested for autografting. The harvested grafts were explant-cultured for 1 week. A second procedure was performed to replant the C6 nerve root using the explant-cultured nerve graft 1 week after the first procedure. Histological and immunohistochemical analyses were performed 8 weeks after the second procedure. We first compared findings between explant-cultured nerve grafts and fresh nerve grafts, following which we compared findings between explant-cultured grafts pretreated with and without resveratrol. Changes induced within nerve grafts by 1 week of explant culture with or without resveratrol were investigated in vitro. RESULTS There was no significant difference in outcomes between 1 week-explant-cultured and fresh nerve grafts. Addition of resveratrol to the explant culture medium resulted in a significant increase in the number and myelin thickness of regenerated axons, and in the number of regenerating motor neurons in the C6 spinal cord segment. In vitro analyses revealed that nerve grafts pretreated with resveratrol exhibited significant increases in glial cell line-derived neurotrophic factor (GDNF) expression and the number of dedifferentiated Schwann cells. CONCLUSIONS Resveratrol may promote axonal regeneration following replantation surgery for the treatment of nerve root avulsion injury; however, further studies are required to verify these findings in humans.