Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate

Despite recent evidence suggesting that nerve transfer techniques help improve clinical outcomes, the underlying manner by which collateral-regenerated nerve enters skeletal muscles to restore an organized pattern of the neuromuscular junction (NMJ) is unclear. To construct the animal models of coll...

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Main Authors: Zhidan Qi, Dongdong Li, Li Li, Dexuan Meng, Jin Deng, Bo Jin, Xinyi Gu, Shen Wang, Chen Huang, Xiaofeng Yin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.795623/full
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author Zhidan Qi
Dongdong Li
Dongdong Li
Li Li
Dexuan Meng
Jin Deng
Bo Jin
Xinyi Gu
Shen Wang
Chen Huang
Xiaofeng Yin
Xiaofeng Yin
author_facet Zhidan Qi
Dongdong Li
Dongdong Li
Li Li
Dexuan Meng
Jin Deng
Bo Jin
Xinyi Gu
Shen Wang
Chen Huang
Xiaofeng Yin
Xiaofeng Yin
author_sort Zhidan Qi
collection DOAJ
description Despite recent evidence suggesting that nerve transfer techniques help improve clinical outcomes, the underlying manner by which collateral-regenerated nerve enters skeletal muscles to restore an organized pattern of the neuromuscular junction (NMJ) is unclear. To construct the animal models of collateral regeneration, the proximal peroneal nerve was fixed to the distal tibial nerve stump. Three months after surgery, the spatial distribution of motor endplates (MEPs) and corresponding in-muscle nerve branches in long flexor digitorum muscles were observed with tissue optical clearing combined with light-sheet microscopy in transgenic fluorescent mice. The results showed that the number of fibers in the proximal donor peroneal nerve was 415 ± 11, while regenerated nerve fibers in the distal tibial stump were 781 ± 43, which indicates a collateral regeneration ratio of 1.88. The spatial distribution of MEPs was restored to an organized pattern of the lamella, and the corresponding in-muscle nerve branches reverted to the normal manner such as after collateral regeneration. Beyond this, the numbers of MEPs dominated by the single distal nerve fiber were 25.58 ± 0.50 and 26.42 ± 0.94, respectively (n = 6, p > 0.05, collateral regeneration group vs. normal group). However, the numbers of distal-regenerated nerve fibers were less than those in normal control groups (781 ± 43 vs. 914 ± 55, n = 6, p < 0.05), and the number and perforations of MEPs were lower than those in normal control groups as such. In summary, this is the first study to show the manner of collateral regeneration of the peripheral nerve that the smaller proximal donor nerve can sprout more axonal buds to connect distal larger nerves and finally restore to an organized pattern of lamella dominated by corresponding in-muscle nerve branches.
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spelling doaj.art-4ab865af9fc8443bb400da94d08453c22022-12-21T19:31:05ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-02-011210.3389/fphys.2021.795623795623Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor EndplateZhidan Qi0Dongdong Li1Dongdong Li2Li Li3Dexuan Meng4Jin Deng5Bo Jin6Xinyi Gu7Shen Wang8Chen Huang9Xiaofeng Yin10Xiaofeng Yin11Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics, PLA Strategic Support Force Medical Center, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaPeking University Third Hospital, Department of Orthopaedics, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, ChinaDepartment of Intelligent Medicine, Pizhou People’s Hospital, Jiangsu, ChinaDespite recent evidence suggesting that nerve transfer techniques help improve clinical outcomes, the underlying manner by which collateral-regenerated nerve enters skeletal muscles to restore an organized pattern of the neuromuscular junction (NMJ) is unclear. To construct the animal models of collateral regeneration, the proximal peroneal nerve was fixed to the distal tibial nerve stump. Three months after surgery, the spatial distribution of motor endplates (MEPs) and corresponding in-muscle nerve branches in long flexor digitorum muscles were observed with tissue optical clearing combined with light-sheet microscopy in transgenic fluorescent mice. The results showed that the number of fibers in the proximal donor peroneal nerve was 415 ± 11, while regenerated nerve fibers in the distal tibial stump were 781 ± 43, which indicates a collateral regeneration ratio of 1.88. The spatial distribution of MEPs was restored to an organized pattern of the lamella, and the corresponding in-muscle nerve branches reverted to the normal manner such as after collateral regeneration. Beyond this, the numbers of MEPs dominated by the single distal nerve fiber were 25.58 ± 0.50 and 26.42 ± 0.94, respectively (n = 6, p > 0.05, collateral regeneration group vs. normal group). However, the numbers of distal-regenerated nerve fibers were less than those in normal control groups (781 ± 43 vs. 914 ± 55, n = 6, p < 0.05), and the number and perforations of MEPs were lower than those in normal control groups as such. In summary, this is the first study to show the manner of collateral regeneration of the peripheral nerve that the smaller proximal donor nerve can sprout more axonal buds to connect distal larger nerves and finally restore to an organized pattern of lamella dominated by corresponding in-muscle nerve branches.https://www.frontiersin.org/articles/10.3389/fphys.2021.795623/fullperipheral nerve injurycollateral regenerationneuromuscular junctionoptical clearinglight-sheet microscopythree-dimensional distributions
spellingShingle Zhidan Qi
Dongdong Li
Dongdong Li
Li Li
Dexuan Meng
Jin Deng
Bo Jin
Xinyi Gu
Shen Wang
Chen Huang
Xiaofeng Yin
Xiaofeng Yin
Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
Frontiers in Physiology
peripheral nerve injury
collateral regeneration
neuromuscular junction
optical clearing
light-sheet microscopy
three-dimensional distributions
title Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
title_full Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
title_fullStr Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
title_full_unstemmed Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
title_short Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
title_sort studies on the manner of collateral regeneration from nerve stem to motor endplate
topic peripheral nerve injury
collateral regeneration
neuromuscular junction
optical clearing
light-sheet microscopy
three-dimensional distributions
url https://www.frontiersin.org/articles/10.3389/fphys.2021.795623/full
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