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HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway.
Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2020-07-26 , DOI: 10.1007/s10571-020-00921-3
Huiqiang Chen 1 , Guoshen Xu 2 , You Wu 1 , Xinyu Wang 1 , Fei Wang 1 , Ying Zhang 1
Affiliation  

Hyperbaric oxygen preconditioning (HBO-PC) has beneficial effects on the promotion of locomotor recovery by reducing apoptosis and inflammation after traumatic spinal cord injury (SCI). The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in apoptosis and inflammation in many pathophysiological conditions. However, whether HBO-PC improves traumatic SCI-induced locomotor dysfunction by regulating the mTOR signaling pathway and its downstream molecules remains unknown. In the present study, we found that HBO-PC significantly promoted SCI-induced hind-limb locomotor recovery and increased the amplitude and potential of motor evoked potential. Magnetic resonance imaging showed that spinal cavitation or atrophy caused by SCI was obviously alleviated by HBO-PC therapy. Histological analysis showed that the changes in spinal cord neural structure in SCI rats were markedly restored by HBO-PC treatment. Western blot analysis showed that the SCI-induced enhanced levels of p-mTOR, inflammatory cytokines and apoptosis in the spinal cord were abrogated after administration of HBO-PC. Furthermore, intrathecal administration of an mTOR agonist reversed the effects of HBO-PC on locomotor function recovery, p-NF-κB p65 and p-p70S6K levels, inflammation and apoptosis. These findings indicated a new mechanism by which HBO-PC therapy suppressed inflammation and apoptosis through inactivation of the mTOR signaling pathway, which contributed to motor disability in SCI rats.



中文翻译:


HBO-PC 通过减少 SCI 大鼠的细胞凋亡和炎症来促进运动恢复:mTOR 信号通路的作用。



高压氧预处理(HBO-PC)通过减少创伤性脊髓损伤(SCI)后的细胞凋亡和炎症,对促进运动恢复具有有益作用。哺乳动物雷帕霉素靶点 (mTOR) 信号通路与许多病理生理条件下的细胞凋亡和炎症有关。然而,HBO-PC是否通过调节mTOR信号通路及其下游分子来改善创伤性SCI引起的运动功能障碍仍不清楚。在本研究中,我们发现HBO-PC显着促进SCI诱导的后肢运动恢复,并增加运动诱发电位的幅度和电位。磁共振成像显示,HBO-PC治疗明显减轻了SCI引起的脊髓空洞或萎缩。组织学分析表明,HBO-PC治疗后SCI大鼠脊髓神经结构的变化得到明显恢复。蛋白质印迹分析显示,给予 HBO-PC 后,SCI 诱导的p -mTOR、炎症细胞因子和脊髓细胞凋亡水平升高被消除。此外,鞘内注射 mTOR 激动剂可逆转 HBO-PC 对运动功能恢复、 p -NF-κB p65 和p -p70S6K 水平、炎症和细胞凋亡的影响。这些发现表明了一种新机制,HBO-PC 疗法通过使 mTOR 信号通路失活来抑制炎症和细胞凋亡,从而导致 SCI 大鼠的运动障碍。

更新日期:2020-07-26
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