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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Main Authors: Ming-Wei Lin, Shih-Yuan Fang, Jung-Yu C. Hsu, Chih-Yuan Huang, Po-Hsuan Lee, Chi-Chen Huang, Hui-Fang Chen, Chen-Fuh Lam, Jung-Shun Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2022.800883/full
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author Ming-Wei Lin
Ming-Wei Lin
Ming-Wei Lin
Shih-Yuan Fang
Jung-Yu C. Hsu
Jung-Yu C. Hsu
Chih-Yuan Huang
Po-Hsuan Lee
Chi-Chen Huang
Hui-Fang Chen
Chen-Fuh Lam
Chen-Fuh Lam
Chen-Fuh Lam
Jung-Shun Lee
Jung-Shun Lee
Jung-Shun Lee
author_facet Ming-Wei Lin
Ming-Wei Lin
Ming-Wei Lin
Shih-Yuan Fang
Jung-Yu C. Hsu
Jung-Yu C. Hsu
Chih-Yuan Huang
Po-Hsuan Lee
Chi-Chen Huang
Hui-Fang Chen
Chen-Fuh Lam
Chen-Fuh Lam
Chen-Fuh Lam
Jung-Shun Lee
Jung-Shun Lee
Jung-Shun Lee
author_sort Ming-Wei Lin
collection DOAJ
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 doaj.art-8efba10cad5a4b22bce0052e6c5710202022-12-21T18:59:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-04-011610.3389/fnins.2022.800883800883Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in RatsMing-Wei Lin0Ming-Wei Lin1Ming-Wei Lin2Shih-Yuan Fang3Jung-Yu C. Hsu4Jung-Yu C. Hsu5Chih-Yuan Huang6Po-Hsuan Lee7Chi-Chen Huang8Hui-Fang Chen9Chen-Fuh Lam10Chen-Fuh Lam11Chen-Fuh Lam12Jung-Shun Lee13Jung-Shun Lee14Jung-Shun Lee15Department of Medical Research, E-Da Hospital, E-Da Cancer Hospital, Kaohsiung City, TaiwanDepartment of Nursing, College of Medicine, I-Shou University, Kaohsiung City, TaiwanRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung City, TaiwanDepartment of Anesthesiology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, TaiwanSection of Neurosurgery, Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, TaiwanSection of Neurosurgery, Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, TaiwanSection of Neurosurgery, Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, TaiwanDepartment of Medical Research, E-Da Hospital, E-Da Cancer Hospital, Kaohsiung City, TaiwanDepartment of Anesthesiology, E-Da Hospital, E-Da Cancer Hospital, Kaohsiung City, TaiwanCollege of Medicine, I-Shou University, Kaohsiung City, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, TaiwanSection of Neurosurgery, Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, TaiwanMitochondrial 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.https://www.frontiersin.org/articles/10.3389/fnins.2022.800883/fullallogenic mitochondriamitochondrial dysfunctionmitochondrial transplantationoxidative stressspinal cord injury
spellingShingle Ming-Wei Lin
Ming-Wei Lin
Ming-Wei Lin
Shih-Yuan Fang
Jung-Yu C. Hsu
Jung-Yu C. Hsu
Chih-Yuan Huang
Po-Hsuan Lee
Chi-Chen Huang
Hui-Fang Chen
Chen-Fuh Lam
Chen-Fuh Lam
Chen-Fuh Lam
Jung-Shun Lee
Jung-Shun Lee
Jung-Shun Lee
Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
Frontiers in Neuroscience
allogenic mitochondria
mitochondrial dysfunction
mitochondrial transplantation
oxidative stress
spinal cord injury
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 allogenic mitochondria
mitochondrial dysfunction
mitochondrial transplantation
oxidative stress
spinal cord injury
url https://www.frontiersin.org/articles/10.3389/fnins.2022.800883/full
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