HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway

HBO-PC通过减少脊髓损伤大鼠的细胞凋亡和炎症来促进运动功能恢复:mTOR信号通路的作用

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作者:Huiqiang Chen #, Guoshen Xu #, You Wu, Xinyu Wang, Fei Wang, Ying Zhang

Abstract

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.

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