Experimental study on the protective effects of edaravone against ischemic spinal cord injury

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

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Delayed ischemic spinal cord injury after total en bloc spondylectomy in the thoracic spine

Journal of Orthopaedic Science ◽

10.1016/j.jos.2020.12.008 ◽

2021 ◽

Author(s):

Yeong Huei Ng ◽

Satoshi Kato ◽

Satoru Demura ◽

Kazuya Shinmura ◽

Noriaki Yokogawa ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Thoracic Spine ◽

En Bloc ◽

Total En Bloc Spondylectomy ◽

En Bloc Spondylectomy ◽

Bloc Spondylectomy ◽

Cord Injury ◽

Ischemic Spinal Cord Injury

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The experimental study of hypoxia-inducible factor-1α and its target genes in spinal cord injury

Spinal Cord ◽

10.1038/sj.sc.3101813 ◽

2005 ◽

Vol 44 (1) ◽

pp. 35-43 ◽

Cited By ~ 31

Author(s):

H Xiaowei ◽

Z Ninghui ◽

X Wei ◽

T Yiping ◽

X Linfeng

Keyword(s):

Spinal Cord ◽

Experimental Study ◽

Spinal Cord Injury ◽

Target Genes ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1Α ◽

Cord Injury

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Neuroprotective Effect of Epidural Electrical Stimulation against Ischemic Spinal Cord Injury in Rats

Anesthesiology ◽

10.1097/00000542-200507000-00015 ◽

2005 ◽

Vol 103 (1) ◽

pp. 84-92 ◽

Cited By ~ 10

Author(s):

Manabu Kakinohana ◽

Hideki Harada ◽

Yasunori Mishima ◽

Tatsuhiko Kano ◽

Kazuhiro Sugahara

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Electrical Stimulation ◽

Neuroprotective Effect ◽

Spinal Cord Ischemia ◽

Aortic Occlusion ◽

Cord Injury ◽

Optimal Setting ◽

Transient Aortic Occlusion ◽

Ischemic Spinal Cord Injury

Background Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion. Methods Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia. Results Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group. Conclusions Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.

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Transforaminal Lumbar and Thoracic Interventions and Ischemic Spinal Cord Injury

10.2310/pm.15001 ◽

2016 ◽

Author(s):

Scott E. Glaser ◽

Rinoo Shah

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Spinal Cord Infarction ◽

Supporting Evidence ◽

Steroid Injections ◽

Epidural Steroid Injections ◽

Root Cause ◽

Cord Injury ◽

Epidural Steroid ◽

Ischemic Spinal Cord Injury

Transforaminal epidural steroid injections have been shown to be associated with catastrophic neurologic complications secondary to spinal cord infarction. The reflexive, ad hoc response of practitioners to these injuries has been to recommend risk minimization strategies to prevent embolism of the injected particulate steroids and to use nonparticulate steroids. This focus on distal embolism as the sole or primary cause of catastrophic outcomes lacks conclusive supporting evidence and does not suffice to protect the patient from paraplegia as it fails to address the root cause of the complications. A root cause analysis of the procedure provides evidence that the injection technique itself—the “safe triangle”—creates a risk of arterial damage and sequelae leading to ischemia of the spinal cord. The evidence is strong that the only way to mitigate or eliminate the risk of paraplegia is to use a different technique to perform transforaminal injections: the Kambin triangle approach. This change in technique is the only definitive solution that addresses the root cause of these catastrophic sequelae associated with transforaminal epidural steroid injections. Key Words: Artery of Adamkiewicz, ischemic spinal cord injury, Kambin triangle, safe triangle, transforaminal epidural injection

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