Activation of SIRT1 by hyperbaric oxygenation promotes recovery of motor dysfunction in spinal cord injury rats

Abstract

Background Hyperbaric oxygenation (HBO) therapy can improve locomotor dysfunction following spinal cord injury (SCI). Emerging evidence has demonstrated that sirtuin1 (SIRT1) exerts protective effects on neurons. However, whether HBO alleviates locomotor dysfunction by regulating SIRT1 is unclear. Methods The traumatic SCI animal model was performed on the adult Sprague-Dawley rats. The Basso, Beattie Bresnahan (BBB) locomotor rating scale was used to evaluate the open-field locomotor function. Western blot, real-time quantitative reverse transcription polymerase chain reaction, SIRT1 activity assay, and enzyme-linked immunosorbent assays were performed to explore the molecular mechanisms. Results We found that series HBO therapy significantly improved locomotor dysfunction and ameliorated the decreased mRNA, protein, and activity of spinal cord SIRT1 induced by traumatic SCI injury in rats. In addition, intraperitoneal injection of SIRT1 inhibitor EX-527 abolished the beneficial effects of series HBO treatment on locomotor deficits. Importantly, series HBO treatment following the traumatic SCI injury inhibited the inflammatory cascade and apoptosis-related protein, which was retained by EX-527 and enhanced by SRT1720. Furthermore, EX-527 blocked the enhanced induction of autophagy series with the HBO application. Conclusion These findings demonstrated a new mechanism for series HBO therapy involving activation of SIRT1 and subsequent modulation of the inflammatory cascade, apoptosis, and autophagy, which contributed to the recovery of motor dysfunction.