Prevention of Axonal Degeneration by Perineurium Injection of Mitochondria in a Sciatic Nerve Crush Injury Model

坐骨神经挤压伤模型中神经束膜注射线粒体预防轴突变性

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作者:Chi-Chung Kuo, Hong-Lin Su, Tzu-Lin Chang, Chien-Yi Chiang, Meei-Ling Sheu, Fu-Chou Cheng, Chun-Jung Chen, Jason Sheehan, Hung-Chuan Pan

Background

Axon degeneration leads to cytoskeletal disassembly, metabolism imbalance, and mitochondrial dysfunction during neurodegeneration or nerve injury.

Conclusion

Mitochondria injection can protect injured nerves from axonal degeneration both in Vitro and in Vivo. This improvement was accompanied with the expression of neurotrophic factors as well as the reduction of oxidative stress, which may account for the functional recovery of both injured nerves and denervated muscles.

Methods

Sciatic nerve explants cocultured with mitochondria were assessed for the optimal dosage in local injection and nerve regeneration potential. The left sciatic nerve was crushed in Sprague-Dawley rats and then local injection of mitochondria into the distal end of the injured nerve was conducted for further assessment.

Objective

In this study, we assess the possibility of mitigating axon degeneration by local injection of mitochondria in a crushed sciatic nerve.

Results

Mitochondrial coculture attenuated cytoskeletal loss and oxidative stress in isolated nerve explants. In Vivo analyses also showed that mitochondrial transplantation improved animal neurobehaviors, electrophysiology of nerve conduction, and muscle activities. Mitochondria injection significantly attenuated the oxidative stress and increased the expression of neurotrophic factors both in injured nerves and denervated muscles, as well as restored muscular integrity, and increased the pool of muscular progenitor cells and total muscle weight.

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