Abstract
Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.
Highlights
Spinal cord injury (SCI) has become a major health issue of global concern
To observe the effects of surgical decompression and RAPA on intramedullary pressure (IMP) after SCI, we monitored the IMP in the normal (N), SCI, rapamycin (R), surgical decompression (DE), and rapamycin combined with surgical decompression (R-DE) treatment groups (Fig. 1a)
There were no significant changes in the R-DE group compared to DE group, indicating that RAPA may not have a significant impact on IMP (Fig. 1b)
Summary
Spinal cord injury (SCI) has become a major health issue of global concern. Even with the current major clinical interventions for patients, such as surgical decompression, stem cell therapy, neurotrophic factor treatment, and platelet-rich plasma treatment, nerve damage is difficult to repair. Decompression after SCI is a conventional treatment method[2] and has been proven to have significant beneficial effects. This method releases pressure on the swollen spinal cord, increases spinal blood perfusion, reduces secondary injuries, and improves nerve function[3,4,5,6,7]. There is an urgent need to develop a simple and feasible therapy for the emergency treatment of patients with SCI before surgery
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