Contusion, dislocation, and distraction: primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury

2007 ◽  
Vol 6 (3) ◽  
pp. 255-266 ◽  
Author(s):  
Anthony M. Choo ◽  
Jie Liu ◽  
Clarrie K. Lam ◽  
Marcel Dvorak ◽  
Wolfram Tetzlaff ◽  
...  

Object In experimental models of spinal cord injury (SCI) researchers have typically focused on contusion and transection injuries. Clinically, however, other injury mechanisms such as fracture–dislocation and distraction also frequently occur. The objective of the present study was to compare the primary damage in three clinically relevant animal models of SCI. Methods Contusion, fracture–dislocation, and flexion–distraction animal models of SCI were developed. To visualize traumatic increases in cellular membrane permeability, fluorescein–dextran was infused into the cerebrospi-nal fluid prior to injury. High-speed injuries (approaching 100 cm/second) were produced in the cervical spine of deeply anesthetized Sprague–Dawley rats (28 SCI and eight sham treated) with a novel multimechanism SCI test system. The animals were killed immediately thereafter so that the authors could characterize the primary injury in the gray and white matter. Sections stained with H & E showed that contusion and dislocation injuries resulted in similar central damage to the gray matter vasculature whereas no overt hemorrhage was detected following distraction. Contusion resulted in membrane disruption of neuronal somata and axons localized within 1 mm of the lesion epicenter. In contrast, membrane compromise in the dislocation and distraction models was observed to extend rostrally up to 5 mm, particularly in the ventral and lateral white matter tracts. Conclusions Given the pivotal nature of hemorrhagic necrosis and plasma membrane compromise in the initiation of downstream SCI pathomechanisms, the aforementioned differences suggest the presence of mechanism-specific injury regions, which may alter future clinical treatment paradigms.

2021 ◽  
pp. 197140092110268
Author(s):  
Seyedeh Niloufar Rafiei Alavi ◽  
Arian Madani Neishaboori ◽  
Mahmoud Yousefifard

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sheng-Yu Cui ◽  
Wei Zhang ◽  
Zhi-Ming Cui ◽  
Hong Yi ◽  
Da-Wei Xu ◽  
...  

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.


2014 ◽  
Vol 21 (3) ◽  
pp. 454-457 ◽  
Author(s):  
Timothy J. Kovanda ◽  
Eric M. Horn

Secondary injury following initial spinal cord trauma is uncommon and frequently attributed to mismanagement of an unprotected cord in the acute time period after injury. Subacute posttraumatic ascending myelopathy (SPAM) is a rare occurrence in the days to weeks following an initial spinal cord injury that is unrelated to manipulation of an unprotected cord and involves 4 or more vertebral levels above the original injury. The authors present a case of SPAM occurring in a 15-year-old boy who sustained a T3–4 fracture-dislocation resulting in a complete spinal cord injury, and they highlight the imaging findings and optimum treatment for this rare event.


2007 ◽  
Vol 58 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Joong Hee Kim ◽  
David N. Loy ◽  
Hsiao-Fang Liang ◽  
Kathryn Trinkaus ◽  
Robert E. Schmidt ◽  
...  

Author(s):  
Marie-Helene Beausejour ◽  
Eric Wagnac ◽  
Pierre-Jean Arnoux ◽  
Jean-Marc Mac-Thiong ◽  
Yvan Petit

Abstract Flexion-distraction injuries frequently cause traumatic cervical spinal cord injury (SCI). Post-traumatic instability can cause aggravation of the secondary SCI during patient's care. However, there is little information on how the pattern of disco-ligamentous injury affects the SCI severity and mechanism. This study objective was to analyze how different flexion-distraction disco-ligamentous injuries affect the SCI mechanisms during post-traumatic flexion and extension. A cervical spine finite element model including the spinal cord was used and different combinations of partial or complete intervertebral disc (IVD) rupture and disruption of various posterior ligaments were modeled at C4-C5, C5-C6 or C6-C7. In flexion, complete IVD rupture combined with posterior ligamentous complex rupture was the most severe injury leading to the most extreme von Mises stress (47 to 66 kPa), principal strains p1 (0.32 to 0.41 in white matter) and p3 (-0.78 to -0.96 in white matter) in the spinal cord and to the most important spinal cord compression (35 to 48 %). The main post-trauma SCI mechanism was identified as compression of the anterior white matter at the injured level combined with distraction of the posterior spinal cord during flexion. There was also a concentration of the maximum stresses in the gray matter after injury. Finally, in extension, the injuries tested had little impact on the spinal cord. The capsular ligament was the most important structure in protecting the spinal cord. Its status should be carefully examined during patient's management.


Author(s):  
Kest Verstappen ◽  
René Aquarius ◽  
Alexey Klymov ◽  
Kimberley E. Wever ◽  
Lyan Damveld ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1018 ◽  
Author(s):  
Volker Dietz

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.


2018 ◽  
Vol 33 (3) ◽  
pp. 240-251
Author(s):  
S. Wilson ◽  
S. J. Nagel ◽  
L. A. Frizon ◽  
D. C. Fredericks ◽  
N. A. DeVries-Watson ◽  
...  

2021 ◽  
Author(s):  
Zheng Cao ◽  
Weitao Man ◽  
Yuhui Xiong ◽  
Yi Guo ◽  
Shuhui Yang ◽  
...  

Abstract A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact, and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.


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