Non-Coding RNAs: Emerging Therapeutic Targets in Spinal Cord Ischemia-Reperfusion Injury.

Xiao Ling,Jun Lu,Hanjun Qin,Shaoyi Zheng,Pengyu Zhou,Jun Yang,Xingqi Zhao,Peng Zhu

doi:10.3389/fneur.2021.680210

Abstract

Paralysis or paraplegia caused by transient or permanent spinal cord ischemia–reperfusion injury (SCIRI) remains one of the most devastating post-operative complications after thoracoabdominal aortic surgery, even though perioperative strategies and surgical techniques continue to improve. Uncovering the molecular and cellular pathophysiological processes in SCIRI has become a top priority. Recently, the expression, function, and mechanism of non-coding RNAs (ncRNAs) in various diseases have drawn wide attention. Non-coding RNAs contain a variety of biological functions but do not code for proteins. Previous studies have shown that ncRNAs play a critical role in SCIRI. However, the character of ncRNAs in attenuating SCIRI has not been systematically summarized. This review article will be the first time to assemble the knowledge of ncRNAs regulating apoptosis, inflammation, autophagy, and oxidative stress to attenuate SCIRI. A better understanding of the functional significance of ncRNAs following SCIRI could help us to identify novel therapeutic targets and develop potential therapeutic strategies. All the current research about the function of nRNAs in SCIRI will be summarized one by one in this review.

Highlights

Up to 45% of the reported cases of spinal cord ischemia–reperfusion injury (SCIRI) were attributed to an iatrogenic cause [1]
Because of the organ-specific effect of NOX4 in neurons and blood–brain barrier endothelial cells, NOX4 is highly sensitive to cerebral ischemic damage [79]. Zhao and his colleagues found that pretreatment with miRNA-25-enriched exosomes by intrathecal injection diminished NOX4 expression in SCIRI rats, elevated superoxide dismutase activity, and decreased the levels of tumor necrosis factor (TNF)-α, IL-1b, and malondialdehyde content in spinal cords, giving better neuroprotective effects [42]
It has been demonstrated that hydrogen sulfide (NaSH) preprocessing can decrease the spinal cord infarct zone in a SCIRI rat model and reduce the apoptosis rate in the SH5YSY cells treated with oxygen-glucose deprivation (OGD)/R

Summary

Introduction

Up to 45% of the reported cases of spinal cord ischemia–reperfusion injury (SCIRI) were attributed to an iatrogenic cause [1]. Bcl2, B-cell lymphoma-2; ECE1, endothelin-converting enzyme 1; Ern1, endoplasmic reticulum to nucleus signaling 1; HMGB1, high-mobility group box-1; iASPP, inhibitory member of the apoptosis-stimulating proteins of p53 family; Mfsd2a, major facilitator superfamily domain containing 2a; OGD/R, oxygen-glucose deprivation/reoxygenation; PDCD4, programmed cell death 4; SCIRI, spinal cord ischemia-reperfusion injury; SD rats, Sprague-Dawley rats; SIRT1, sirtuin 1; TLR3, Toll-like receptor-3; TLR4, Toll-like receptor-4.

Results

Conclusion