Transplantation of viable mitochondria attenuates neurologic injury after spinal cord ischemia

Shih Yuan Fang, Jun Neng Roan, Jung Shun Lee, Meng Hsuan Chiu, Ming Wei Lin, Chien Cheng Liu, Chen Fuh Lam

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

摘要

Objectives: Spinal cord ischemia (SCI) is one of the major concerns of postoperative paraplegia during major vascular or aortic surgery. Since mitochondrial dysfunction develops at the early stage of SCI, this study tested the neuronal protective effect of transplantation of viable mitochondria to the ischemic cord in rats. Methods: SCI was induced by crossclamping of thoracic aorta at T6 level for 25 minutes, followed by release of vascular clip to restore aortic blood flow in the anesthetized rats. Mitochondria (100 μg) were isolated from freshly harvested soleus muscle and delivered via the internal jugular vein before releasing of vascular clip. The motor function was assessed independently up to 7 days after reperfusion. Spinal cords were harvested and analyzed for molecular and histological changes. Results: Whole-body in vivo images acquired by an in vivo imaging system confirmed the enhancement of MitoTracker fluorescence at the regions below crossclamping and in the ischemic cord. Compared with control vehicles, transplantation of mitochondria significantly improved the lower-limb locomotor function of rats subjected to cord ischemia up to 7 days after surgery. Mitochondrial transplantation suppressed the regional endoplasmic reticulum stress in the ischemic cord by attenuating CCAAT-enhancer-binding protein homologous protein expression and restoring binding immunoglobulin protein levels. In accordance, tissue levels of interleukin-6, tumor necrosis factor-α, and caspase-3 were attenuated in the mitochondrial transplanted group. Histologic examination also showed significant increase in numbers of Nissls bodies in the neurons at the ventral horn of ischemic cord following mitochondrial transplantation. Conclusions: Our study showed that transplantation of freshly isolated mitochondria during the early stage of spinal cord ischemia–reperfusion injury suppressed the oxidative stress in endoplasmic reticulum of the injured cord, thereby reducing neuroapoptosis and improving locomotor function of rats with SCI.

原文English
頁(從 - 到)e337-e347
期刊Journal of Thoracic and Cardiovascular Surgery
161
發行號5
DOIs
出版狀態Published - 2021 五月

All Science Journal Classification (ASJC) codes

  • 手術
  • 肺和呼吸系統醫學
  • 心臟病學與心血管醫學

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