International immunopharmacology · 2024
Edaravone promotes motoneuron survival and functional recovery after brachial plexus root avulsion and reimplantation in rats: Involvement of SIRT1/TFEB pathway.
СтатьяНазвание и аннотация: Перевод в очереди
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Jia Cai-Ju, Chen Man-Ni, Huang Dou-Dou, Wu Shao-Feng, Zeng Chun-Ming, Liu Zhe-Qi, Wang Meng-Xia, Huang Yan-Feng, Yuan Qiu-Ju, Zhang Xie
Аннотация
BACKGROUND: Brachial plexu root avulsion (BPRA) commonly causes extensive motoneuron death, motor axon degeneration and denervation of biceps, leading to devastating motor dysfunction in the upper limb. Edaravone (Eda) has been proven to exert anti-oxidative and neuroprotective effects on various neurological disorders. Herein, we aimed to investigate the efficacy profile and potential mechanisms of Eda on BPRA in vitro and in vivo models.
METHODS: Rats following BPRA and reimplantation surgery were intraperitoneally injected with Eda once daily. The motor function recovery of the affected forelimb was assessed by Terzis grooming test. Histological staining and transmission electron microscopy were performed to evaluate the morphological appearance of the spinal cord, musculocutaneous nerve, and biceps. Further in-depth studies to explore the underlying mechanisms of Eda were conducted using Western blotting, biochemical assays, and immunofluorescence in H2O2-induced NSC-34 cells.
RESULTS: Eda significantly accelerated motor function recovery, enhanced motoneuron survival, prevented motor axon descent, preserved myelin sheath integrity and attenuated muscle atrophy. Additionally, Eda treatment markedly suppressed oxidative stress-related indicators, downregulated apoptosis-related proteins, mitigated glial reactivity, and activated SIRT1 and TFEB. Notably, the neuroprotective effect of Eda was diminished by the SIRT1 inhibitor EX527 in H2O2-treated NSC-34 cells, suggesting that Eda regulated oxidative stress and apoptosis through SIRT1/TFEB-induced autophagy flux.
CONCLUSIONS: Eda enhanced motoneuron survival and axonal regeneration that promotes motor functional restoration by inhibiting oxidative stress and apoptosis via the SIRT1/TFEB-autophagy pathway. Thus, it may serve as a promising strategy in reimplantation surgery for the treatment of BPRA.
METHODS: Rats following BPRA and reimplantation surgery were intraperitoneally injected with Eda once daily. The motor function recovery of the affected forelimb was assessed by Terzis grooming test. Histological staining and transmission electron microscopy were performed to evaluate the morphological appearance of the spinal cord, musculocutaneous nerve, and biceps. Further in-depth studies to explore the underlying mechanisms of Eda were conducted using Western blotting, biochemical assays, and immunofluorescence in H2O2-induced NSC-34 cells.
RESULTS: Eda significantly accelerated motor function recovery, enhanced motoneuron survival, prevented motor axon descent, preserved myelin sheath integrity and attenuated muscle atrophy. Additionally, Eda treatment markedly suppressed oxidative stress-related indicators, downregulated apoptosis-related proteins, mitigated glial reactivity, and activated SIRT1 and TFEB. Notably, the neuroprotective effect of Eda was diminished by the SIRT1 inhibitor EX527 in H2O2-treated NSC-34 cells, suggesting that Eda regulated oxidative stress and apoptosis through SIRT1/TFEB-induced autophagy flux.
CONCLUSIONS: Eda enhanced motoneuron survival and axonal regeneration that promotes motor functional restoration by inhibiting oxidative stress and apoptosis via the SIRT1/TFEB-autophagy pathway. Thus, it may serve as a promising strategy in reimplantation surgery for the treatment of BPRA.