• Meei-Ling Sheu, Chiung-Chyi Shen, Hsi-Kai Tsou, Meng Yin Yang, Hong-Lin Su, Jason Sheehan, Ming-Hong Chang, Hong-Shiu Chen, and Hung-Chuan Pan.
• Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.
• Neurosurgery. 2021 Jun 15; 89 (1): E49-E59.

BackgroundPeripheral nerve injuries result in muscle denervation and apoptosis of the involved muscle, which subsequently reduces mitochondrial content and causes muscle atrophy. The local injection of mitochondria has been suggested as a useful tool for restoring the function of injured nerves or the brain.ObjectiveTo determine outcomes following the administration of isolated mitochondria into denervated muscle after nerve injury that have not been investigated.MethodsMuscle denervation was conducted in a sciatic nerve crushed by a vessel clamp and the denervated gastrocnemius muscle was subjected to 195 μg hamster green fluorescent protein (GFP)-mitochondria intramuscular infusion for 10 min.ResultsThe mitochondria were homogeneously distributed throughout the denervated muscle after intramuscular infusion. The increases in caspase 3, 8-oxo-dG, Bad, Bax, and ratio of Bax/Bcl-2 levels in the denervated muscle were attenuated by mitochondrial infusion, and the downregulation of Bcl-2 expression was prevented by mitochondrial infusion. In addition, the decrease in the expression of desmin and the acetylcholine receptor was counteracted by mitochondrial infusion; this effect paralleled the amount of distributed mitochondria. The restoration of the morphology of injured muscles and nerves was augmented by the local infusion of mitochondria. Mitochondrial infusion also led to improvements in sciatic functional indexes, compound muscle action potential amplitudes, and conduction latencies as well as the parameters of CatWalk (Noldus) gait analysis.ConclusionThe local infusion of mitochondria can successfully prevent denervated muscle atrophy and augment nerve regeneration by reducing oxidative stress in denervated muscle.© Congress of Neurological Surgeons 2021.

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