摘要
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 200μM 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.
基金
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
Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China,No.N201904(all to JG).