Effects of Brain-Derived Mitochondria on the Function of Neuron and Vascular Endothelial Cell After Traumatic Brain Injury.

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.