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Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats

Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI rema...

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Autores principales: Lin, Ming-Wei, Fang, Shih-Yuan, Hsu, Jung-Yu C., Huang, Chih-Yuan, Lee, Po-Hsuan, Huang, Chi-Chen, Chen, Hui-Fang, Lam, Chen-Fuh, Lee, Jung-Shun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039257/
https://www.ncbi.nlm.nih.gov/pubmed/35495036
http://dx.doi.org/10.3389/fnins.2022.800883
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author Lin, Ming-Wei
Fang, Shih-Yuan
Hsu, Jung-Yu C.
Huang, Chih-Yuan
Lee, Po-Hsuan
Huang, Chi-Chen
Chen, Hui-Fang
Lam, Chen-Fuh
Lee, Jung-Shun
author_facet Lin, Ming-Wei
Fang, Shih-Yuan
Hsu, Jung-Yu C.
Huang, Chih-Yuan
Lee, Po-Hsuan
Huang, Chi-Chen
Chen, Hui-Fang
Lam, Chen-Fuh
Lee, Jung-Shun
author_sort Lin, Ming-Wei
collection PubMed
description Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-μg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI.
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spelling pubmed-90392572022-04-27 Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats Lin, Ming-Wei Fang, Shih-Yuan Hsu, Jung-Yu C. Huang, Chih-Yuan Lee, Po-Hsuan Huang, Chi-Chen Chen, Hui-Fang Lam, Chen-Fuh Lee, Jung-Shun Front Neurosci Neuroscience Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-μg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI. Frontiers Media S.A. 2022-04-12 /pmc/articles/PMC9039257/ /pubmed/35495036 http://dx.doi.org/10.3389/fnins.2022.800883 Text en Copyright © 2022 Lin, Fang, Hsu, Huang, Lee, Huang, Chen, Lam and Lee. https://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
Lin, Ming-Wei
Fang, Shih-Yuan
Hsu, Jung-Yu C.
Huang, Chih-Yuan
Lee, Po-Hsuan
Huang, Chi-Chen
Chen, Hui-Fang
Lam, Chen-Fuh
Lee, Jung-Shun
Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title_full Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title_fullStr Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title_full_unstemmed Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title_short Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
title_sort mitochondrial transplantation attenuates neural damage and improves locomotor function after traumatic spinal cord injury in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039257/
https://www.ncbi.nlm.nih.gov/pubmed/35495036
http://dx.doi.org/10.3389/fnins.2022.800883
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