Baoliang Zhang1, Yalong Gao2, Qifeng Li2, Dongdong Sun3, Xinlong Dong2, Xiaotian Li2, Wenqiang Xin2, Jianning Zhang4. 1. Department of General Medicine, Tianjin Medical University General Hospital, Tianjin, China; Department of Medical Cosmetology, Airport Hospital, Tianjin Medical University General Hospital, Tianjin, China. 2. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education in China and Tianjin Neurological Institute, Tianjin, China. 3. Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China. 4. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education in China and Tianjin Neurological Institute, Tianjin, China. Electronic address: jianningzhang@hotmail.com.
Abstract
OBJECTIVE: Mitochondrial dysfunction plays an essential role in secondary brain injury following traumatic brain injury (TBI). Interestingly, accumulating evidence has shown that therapeutic benefits of mitochondrial transplantation exist. Therefore, we hypothesized that the injection of exogenous mitochondria would contribute to the mitigation of cellular energy metabolism disorders and neurologic functions after TBI. METHODS: We first extracted isolated mitochondria from fresh brain tissue using a kit and then identified their activity and purity. The role of exogenous mitochondria was assessed using the glucose oxygen deprivation-induced cellular damage model and controlled cortical impact-induced mice with TBI. RESULTS: The results showed that treatment with exogenous mitochondria improved the cellular respiratory control rate, the expression of tight junction-associated proteins, and synaptic plasticity-related proteins in vitro. Moreover, the application of exogenous mitochondria significantly reduced cellular apoptosis, promoted angiogenesis and alleviated brain edema and blood-brain barrier leakage in mice subjected to TBI. Additionally, exogenous mitochondria significantly reduced excessive inhibition of long-term depression in the hippocampus 7 days after TBI. CONCLUSIONS: Taken together, the data suggested that exogenous mitochondrial intervention ameliorated glucose oxygen deprivation-induced cell damage and controlled cortical impact-induced TBI in a mouse model. The new discovery in the current study inspires us to suggest that mitochondrial transplantation might serve as a new therapeutic strategy for TBI.
OBJECTIVE: Mitochondrial dysfunction plays an essential role in secondary brain injury following traumatic brain injury (TBI). Interestingly, accumulating evidence has shown that therapeutic benefits of mitochondrial transplantation exist. Therefore, we hypothesized that the injection of exogenous mitochondria would contribute to the mitigation of cellular energy metabolism disorders and neurologic functions after TBI. METHODS: We first extracted isolated mitochondria from fresh brain tissue using a kit and then identified their activity and purity. The role of exogenous mitochondria was assessed using the glucose oxygen deprivation-induced cellular damage model and controlled cortical impact-induced mice with TBI. RESULTS: The results showed that treatment with exogenous mitochondria improved the cellular respiratory control rate, the expression of tight junction-associated proteins, and synaptic plasticity-related proteins in vitro. Moreover, the application of exogenous mitochondria significantly reduced cellular apoptosis, promoted angiogenesis and alleviated brain edema and blood-brain barrier leakage in mice subjected to TBI. Additionally, exogenous mitochondria significantly reduced excessive inhibition of long-term depression in the hippocampus 7 days after TBI. CONCLUSIONS: Taken together, the data suggested that exogenous mitochondrial intervention ameliorated glucose oxygen deprivation-induced cell damage and controlled cortical impact-induced TBI in a mouse model. The new discovery in the current study inspires us to suggest that mitochondrial transplantation might serve as a new therapeutic strategy for TBI.
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