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Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuropro...

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Autores principales: Liu, Junhao, Li, Ruoyao, Huang, Zucheng, Lin, Junyu, Ji, Wei, Huang, Zhiping, Liu, Qi, Wu, Xiaoliang, Wu, Xiuhua, Jiang, Hui, Ye, Yongnong, Zhu, Qingan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862581/
https://www.ncbi.nlm.nih.gov/pubmed/33551740
http://dx.doi.org/10.3389/fnmol.2020.574041
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author Liu, Junhao
Li, Ruoyao
Huang, Zucheng
Lin, Junyu
Ji, Wei
Huang, Zhiping
Liu, Qi
Wu, Xiaoliang
Wu, Xiuhua
Jiang, Hui
Ye, Yongnong
Zhu, Qingan
author_facet Liu, Junhao
Li, Ruoyao
Huang, Zucheng
Lin, Junyu
Ji, Wei
Huang, Zhiping
Liu, Qi
Wu, Xiaoliang
Wu, Xiuhua
Jiang, Hui
Ye, Yongnong
Zhu, Qingan
author_sort Liu, Junhao
collection PubMed
description Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg(–1)⋅day(–1)). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.
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spelling pubmed-78625812021-02-06 Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice Liu, Junhao Li, Ruoyao Huang, Zucheng Lin, Junyu Ji, Wei Huang, Zhiping Liu, Qi Wu, Xiaoliang Wu, Xiuhua Jiang, Hui Ye, Yongnong Zhu, Qingan Front Mol Neurosci Neuroscience Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg(–1)⋅day(–1)). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment. Frontiers Media S.A. 2021-01-22 /pmc/articles/PMC7862581/ /pubmed/33551740 http://dx.doi.org/10.3389/fnmol.2020.574041 Text en Copyright © 2021 Liu, Li, Huang, Lin, Ji, Huang, Liu, Wu, Wu, Jiang, Ye and Zhu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Liu, Junhao
Li, Ruoyao
Huang, Zucheng
Lin, Junyu
Ji, Wei
Huang, Zhiping
Liu, Qi
Wu, Xiaoliang
Wu, Xiuhua
Jiang, Hui
Ye, Yongnong
Zhu, Qingan
Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title_full Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title_fullStr Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title_full_unstemmed Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title_short Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice
title_sort rapamycin preserves neural tissue, promotes schwann cell myelination and reduces glial scar formation after hemi-contusion spinal cord injury in mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862581/
https://www.ncbi.nlm.nih.gov/pubmed/33551740
http://dx.doi.org/10.3389/fnmol.2020.574041
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