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, Huifang; Lam, Chen-Fuh; Lee, Jung-Shun

doi:10.3389/fnins.2022.800883

Cited by 25 publications

(12 citation statements)

References 63 publications

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“…20 Similarly, in our previous study investigating the therapeutic effects of MT on traumatic spinal cord injury, we found that when viable allogenic mitochondria were administered regionally, they primarily distributed into the surrounding area, with most of these exogenous organelles being located interstitially rather than being taken up by the recipient cells. 23 Given that, the mechanisms underlying how MT attenuates neuroinflammation and apoptosis following traumatic nerve injury necessitate further investigations.…”

Section: Discussionmentioning

confidence: 99%

“…19 Animal studies have proven the beneficial effects of MT on various injuries, including ischemia/reperfusion-induced myocardial injuries, 19,20 brain injury, 21,22 and traumatic spinal cord injury. 23,24 Clinical studies have also shown the effectiveness of MT in helping pediatric patients with heart failure wean off central extracorporeal membrane oxygenation support. 25 Consequently, MT is a potential strategy for treating diseases associated with mitochondrial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation

Huang,

Chiu,

Lee

et al. 2023

Mol Pain

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Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats’ spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation

Huang,

Chiu,

Lee

et al. 2023

Mol Pain

Self Cite

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“…In a parallel investigation, intraparenchymal infusion of allogeneic soleus muscles mitochondria into injured spinal cords resulted in the recovery of locomotor and sensory functions in rats with a reduction in SCI-induced cellular apoptosis and inflammation. 421 Additionally, bone marrow stromal cells (BMSCs) have been observed to confer protection against SCI, attributed to their capacity to transfer mitochondria to injured neurons via intercellular gap junctions. 422 Further advancements include the development of an engineered mitochondrial compound specifically designed to target macrophages within the SCI region.…”

Section: Therapeutics For Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial dysfunction: mechanisms and advances in therapy

Zong,

Li,

Liao

et al. 2024

Sig Transduct Target Ther

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Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

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“…Wei et al observed neural damage attenuation and locomotor function improvement in rats. 88 (2) Parthanatos in SCI It is a type of caspase-independent PCD activated upon specific types of DNA due to the hyperactivation of the DNA repair gene poly ADP-ribose polymerase 1 (PARP1). 89 Poly-ADP ribose is (PAR) produced by PARP1 that translocates from the nucleus to the cytoplasm, interacting with mitochondrial proteins and releasing apoptosis-inducing factors (AIFs).…”

Section: ) Mitochondria-mediated (1) Mitoptosis In Scimentioning

confidence: 99%

Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury

Guha¹,

Singh²,

Kumar³

2023

Neurospine

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Cell death is a systematic/nonsystematic process of cessation of normal morphology and functional properties of the cell to replace and recycle old cells with new also promoting inflammation in some cases. It is a complicated process comprising multiple pathways. Some are well-explored, and others have just begun to be. The research on appropriate control of cell death pathways after acute and chronic damage of neuronal cells is being widely researched today due to the lack of regeneration and recovering potential of a neuronal cell after sustaining damage and the inability to control the direction of neuronal growth. In the progression and onset of various neurological diseases, impairments in programmed cell death signaling processes, like necroptosis, apoptosis, ferroptosis, pyroptosis, and pathways directly or indirectly linked, like autophagy as in nonprogrammed necrosis, are observed. Spinal cord injury (SCI) involves the temporary or permanent disruption of motor activities due to the death of a neuronal and glial cell in the spinal cord accompanied by axonal degeneration. Recent years have seen a significant increase in research on the intricate biochemical interactions that occur after a SCI. Different cell death pathways may significantly impact the subsequent damage processes that lead to the eventual neurological deficiency after an injury to the spinal cord. A better knowledge of the molecular basis of the involved cell death pathways might help enhance neuronal and glial survival and neurological deficits, promoting a curative path for SCI.

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

Cited by 25 publications

References 63 publications

Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation

Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation

Mitochondrial dysfunction: mechanisms and advances in therapy

Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury

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