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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Frontiers Media S.A.
2022-04-01
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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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language | English |
last_indexed | 2024-12-21T14:54:02Z |
publishDate | 2022-04-01 |
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series | Frontiers in Neuroscience |
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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