Transplantation of BHK cell derived mitochondria ameliorates nerve dysfunction in sciatic nerve crush model

• Main Authors: Tzu-Lin Chang, 張滋麟
• Other Authors: Hong-Lin Su
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/98519267292977943637

碩士 === 國立中興大學 === 生命科學系所 === 103 === Purpose：Axon degeneration, leads to cytoskeletal disassembly and metabolism imbalance in cells, is characterized in neurodegenerative diseases and nerve injury. Recent researches indicate that mitochondrial function and distribution is a major contributor in axon degeneration process. In 2013, Akihiro Masuzawa et al showed that the injection of mitochondria can restores functional recovery in heart with ischemia-reperfusion injury. The results inspire us to inject mitochondria extracted from BHK-21 cells into sciatic nerve in sciatic nerve crush model and assess the ability that mitochondria ameliorate nerve dysfunction. Materials and methods：Sprague-Dawley rats weighting 200-250 gram are enrolled in our research. Sciatic nerve was crushed for 20 minutes to trigger axon degeneration and 200 microgram of mitochondria was injected into distal end of sciatic nerve. Animal behaviors, nerve function and muscle tissue was observed for 7 and 28 days. Sciatic nerve explant culture was also isolated to estimate mitochondrial effect in axon degeneration. Results：Injection of mitochondria can reduce cytoskeletal loss and oxidative stress. Mitochondrial transplantation improved animal behaviors performance, determined by SFI, Von Frey, Catwalk gait analysis as well as nerve conduction and compound muscle action potential. BDNF, NT-3, CNTF , NF and S100 were highly expressed and CD68 and 8-oxodG were down-regulated, comparing that of to control after injection. Several neurotrophic factors were also increased in muscle. The treated muscle also show with less loss of muscle atrophy as well as improvement of AChR and Desmin. Conclusion：Mitochondrial transplantation in distal end can protect nerve from injury and maintain axons and Schwann cells, which enable nerve of crushed nerve to express neurotrophic factors promote nerve regeneration and inhibit cell death.