<p>Experimental Study on the Role of Apelin-13 in Alleviating Spinal Cord Ischemia Reperfusion Injury Through Suppressing Autophagy</p>

Abstract

Background: This study aimed to explore the effect of Apelin-13 in protecting rats against spinal cord ischemia reperfusion injury (SCIR), as well as the related molecular mechanisms. Methods: One week prior to the experiment, experimental Sprague-Dawley rats were injected with Apelin-13 and the autophagy activator rapamycin through the tail vein once a day for 7 consecutive days. The SCIR rat model was prepared through the abdominal aorta clamping method. At 72 h after injury, the spinal cord tissue water content, infarct volume, and normal neuron count were determined to evaluate the degree of spinal cord tissue injury in the rats. The Basso-Beattie-Bresnahan scoring standard was adopted for functional scoring of the rat hind leg, to reflect the post-injury motor function. At 72 h after injury, changes in mitochondrial membrane potential, reactive oxygen species content, and mitochondrial ATP were detected. ELISA was carried out to detect the malonaldehyde content, as well as catalase, superoxide dismutase, and glutathione catalase activities in spinal cord tissues at 72 h after injury. Quantitative chemistry was conducted to examine the contents of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) in spinal cord tissues. Finally, the expression of autophagy-related proteins, Beclin1, ATG5, and LC3, in spinal cord tissues was detected through the Western blotting assay. Results: Apelin-13 pretreatment alleviated SCIR, promoted motor function recovery, suppressed mitochondrial dysfunction, resisted oxidative stress, and inhibited autophagy in spinal cord tissues following ischemia reperfusion injury. Conclusion: Apelin-3 exerts protection against SCIR by suppressing autophagy.

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

“…Patients who have undergone thoracic and abdominal aortic surgery are frequently faced with nerve injury induced by spinal cord ischemia, which is driven by ROS-induced neuronal apoptosis, neuroinflammation, and autophagy [157]. The intraperitoneal injection of apelin-13 exerted spinal cord protection and recovery of motor function in rats by suppressing autophagy, oxidative stress, and mitochondrial dysfunction [158].…”

Antibiotics with therapeutic effects on spinal cord injury: a review

“…A case report by Clanton et al in 1999 revealed that erythromycin lactobionate, a macrolide with gastrointestinal prokinetic properties, can be used for management of refractory gastroparesis induced by SCI [75]. Later, it was shown that erythromycin exerts neuroprotective effects in rodents and swine undergoing cerebral ischemia–reperfusion [76,77]. In a model of cerebral ischemia–reperfusion injury, it was also indicated that erythromycin significantly reduces oxidative stress and pro‐inflammatory cytokines (e.g., TNF‐α) as well as Ca 2+ ‐binding adapter molecule 1 (IBA‐1) which represents inflammatory microglial activity [51,78].…”

“…It also inhibits mitochondrial protein synthesis in different micro‐organisms such as yeasts [80] and human cells [81]. Considering erythromycin’s anti‐inflammatory and neuroprotective effects and its similar structure with other neuroprotective macrolides (i.e., AZM), investigation, and elucidation of its potential effects on mitochondrial dysfunction and microglial polarization in SCI would be interesting [69,77,82].…”

Identification of the biological function of miR-9 in spinal cord ischemia-reperfusion injury in rats

“…Spinal cord ischemia reperfusion injury (SCII) is a complication occurring under thoracoabdominal aortic or spinal cord surgery, which brings the risk of paralysis and paraplegia (Li et al, 2015a;Xu & Li, 2020). Although various measures were developed and applied to reduce the risks and improve the outcomes of SCII, satisfactory therapeutic…”

“…Spinal cord ischemia reperfusion injury (SCII) is a complication occurring under thoracoabdominal aortic or spinal cord surgery, which brings the risk of paralysis and paraplegia ( Li et al, 2015a ; Xu & Li, 2020 ). Although various measures were developed and applied to reduce the risks and improve the outcomes of SCII, satisfactory therapeutic effects still not be achieved due to multifactorial pathogenic factors ( Ege et al, 2004 ; Fang et al, 2015 ; Li et al, 2014a ; Li et al, 2014b ; Zhou et al, 2013b ).…”