Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (6): 1078-1085.doi: 10.4103/1673-5374.300459

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Ascorbic acid accelerates Wallerian degeneration after peripheral nerve injury

Lixia Li1, 2, 3, Yizhou Xu1, 2, Xianghai Wang1, 2, 5, Jingmin Liu1, 2, 5, Xiaofang Hu1, 2, 5, Dandan Tan1, 2, Zhenlin Li1, Jiasong Guo1, 2, 4, 5, 6, *   

  1. 1 Department of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong Province, China;  2 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong Province, China;  3 Department of Anatomy, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China;  4 Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;  5 Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong Province, China;  6 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Jiasong Guo, PhD, jiasongguo@smu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81870982 & 81571182; the Program for Changjiang Scholars and Innovative Research Team in Universities of China, No. IRT-16R37; the National Key Basic Research Program of China, No. 2014CB542202; the Science and Technology Project of Guangdong Province of China, No. 2015A020212024; Key Research & Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR110104008; the Natural Science Foundation of Guangdong Province of China, No. 2017A030312009, and Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China, No. N201904 (all to JG).

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Abstract: Wallerian degeneration occurs after peripheral nerve injury and provides a beneficial microenvironment for nerve regeneration. Our previous study demonstrated that ascorbic acid promotes peripheral nerve regeneration, possibly through promoting Schwann cell proliferation and phagocytosis and enhancing macrophage proliferation, migration, and phagocytosis. Because Schwann cells and macrophages are the main cells involved in Wallerian degeneration, we speculated that ascorbic acid may accelerate this degenerative process. To test this hypothesis, 400 mg/kg ascorbic acid was administered intragastrically immediately after sciatic nerve transection, and 200 mg/kg ascorbic acid was then administered intragastrically every day. In addition, rat sciatic nerve explants were treated with 200 μM ascorbic acid. Ascorbic acid significantly accelerated the degradation of myelin basic protein-positive myelin and neurofilament 200-positive axons in both the transected nerves and nerve explants. Furthermore, ascorbic acid inhibited myelin-associated glycoprotein expression, increased c-Jun expression in Schwann cells, and increased both the number of macrophages and the amount of myelin fragments in the macrophages. These findings suggest that ascorbic acid accelerates Wallerian degeneration by accelerating the degeneration of axons and myelin in the injured nerve, promoting the dedifferentiation of Schwann cells, and enhancing macrophage recruitment and phagocytosis. The study was approved by the Southern Medical University Animal Care and Use Committee (approval No. SMU-L2015081) on October 15, 2015. 

Key words: ascorbic acid, axon, macrophage, myelin, peripheral nerve injury, phagocytosis, Schwann cell, Wallerian degeneration