Shih-Yuan Fang1, Jun-Neng Roan2, Jung-Shun Lee3, Meng-Hsuan Chiu1, Ming-Wei Lin4, Chien-Cheng Liu5, Chen-Fuh Lam6. 1. Department of Anesthesiology, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. 2. Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. 3. Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. 4. Department of Medical Research, E-Da Hospital and E-Da Cancer Hospital, Kaohsiung, Taiwan; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, I-Shou University College of Medicine, Kaohsiung, Taiwan. 5. School of Medicine, I-Shou University College of Medicine, Kaohsiung, Taiwan; Department of Anesthesiology, E-Da Hospital and E-Da Cancer Hospital, Kaohsiung, Taiwan. 6. Department of Anesthesiology, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan; School of Medicine, I-Shou University College of Medicine, Kaohsiung, Taiwan; Department of Anesthesiology, E-Da Hospital and E-Da Cancer Hospital, Kaohsiung, Taiwan. Electronic address: ed110208@edah.org.tw.
Abstract
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.
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.
Authors: Miguel A Orrego; Samuel Levy; Cory Kelly; Gianfranco Arroyo; Luz Toribio; Hector H García; Melanie Walker Journal: Rev Peru Med Exp Salud Publica Date: 2021-08-30
Authors: Kei Hayashida; Ryosuke Takegawa; Muhammad Shoaib; Tomoaki Aoki; Rishabh C Choudhary; Cyrus E Kuschner; Mitsuaki Nishikimi; Santiago J Miyara; Daniel M Rolston; Sara Guevara; Junhwan Kim; Koichiro Shinozaki; Ernesto P Molmenti; Lance B Becker Journal: J Transl Med Date: 2021-05-17 Impact factor: 5.531