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线粒体移植减轻大鼠创伤性脊髓损伤后的神经损伤并改善运动功能。

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

作者信息

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

机构信息

Department of Medical Research, E-Da Hospital, E-Da Cancer Hospital, Kaohsiung City, Taiwan.

Department of Nursing, College of Medicine, I-Shou University, Kaohsiung City, Taiwan.

出版信息

Front Neurosci. 2022 Apr 12;16:800883. doi: 10.3389/fnins.2022.800883. eCollection 2022.

Abstract

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.

摘要

线粒体功能障碍是脊髓损伤(SCI)继发性神经炎症反应和神经元死亡的一个标志。尽管基于线粒体的治疗是SCI一种有吸引力的治疗选择,但异体线粒体移植治疗SCI的疗效仍不明确。在此,我们确定了线粒体移植对创伤性SCI大鼠的治疗效果。通过在大鼠T10脊髓上应用动脉瘤夹诱导压迫性SCI。将100μg用荧光追踪剂标记的比目鱼肌源性异体线粒体团注入损伤的脊髓。结果表明,治疗后28天内均可在损伤脊髓中检测到移植的线粒体。接受线粒体移植的大鼠比未接受移植的大鼠表现出更好的运动和感觉功能恢复。线粒体移植组损伤脊髓中发动蛋白相关蛋白1的表达和脱髓鞘严重程度均降低。线粒体移植还减轻了SCI诱导的细胞凋亡和炎症反应。这些发现表明,在SCI早期移植异体线粒体可减少线粒体碎片化、神经细胞凋亡、神经炎症和氧化应激的产生,从而导致创伤性SCI后功能恢复改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1cc/9039257/a8bb08a6ee7f/fnins-16-800883-g001.jpg

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