HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway
Autor: | Huiqiang Chen, Ying Zhang, Wu You, Guoshen Xu, Fei Wang, Xinyu Wang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Agonist medicine.drug_class Apoptosis Inflammation Motor Activity Pharmacology Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals Spinal cord injury Spinal Cord Injuries PI3K/AKT/mTOR pathway Neurons business.industry TOR Serine-Threonine Kinases Recovery of Function Cell Biology General Medicine medicine.disease Spinal cord 030104 developmental biology medicine.anatomical_structure medicine.symptom Signal transduction business Locomotion 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Cellular and Molecular Neurobiology. 41:1537-1547 |
ISSN: | 1573-6830 0272-4340 |
DOI: | 10.1007/s10571-020-00921-3 |
Popis: | 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. |
Databáze: | OpenAIRE |
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