scholarly journals A New and Simple Method for Spinal Cord Injury Induction in Mice

2021 ◽  
Author(s):  
Zahra Zeraatpisheh ◽  
◽  
Esmaeil Mirzaei ◽  
Mohammad Nami ◽  
Hamed Alipour ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Injury ◽  
Treatment Strategies ◽  
Body Part ◽  
Macrophage Infiltration ◽  
Cavity Formation ◽  
Post Injury ◽  
Simple Method ◽  
Cord Injury

Introduction: Spinal cord injury (SCI) is a devastating disease with poor clinical outcomes. Animal models provide great opportunities to expand our horizons in identifying SCI pathophysiological mechanisms and subsequently introducing effective treatment strategies. The present study precisely introduces a new murine contusion model. Methods: A simple, economical and reproducible novel instrument was designed which consists of various sections, including a body part, an immobilization piece and a bar-shaped weight. The injury was inflicted to the spinal cord using an eight-gram weight for 5, 10 or 15 minutes after laminectomy at the T9 level in male C57BL/6 mice. Motor function, cavity formation, cell injury and macrophage infiltration were evaluated 28 days' post injury. Results: The newly designed instrument minimized adverse spinal movement during injury induction. Moreover, no additional devices, such as a stereotaxic apparatus, was required to stabilize the animals during surgical procedure. Locomotor activity was deteriorated after injury. Furthermore, tissue damage and cell injury were exacerbated by increasing the duration of weight exertion. In addition, macrophage infiltration around the injured tissue was observed 28 days’ post injury. Conclusion: This novel apparatus could induce a controllable SCI with a clear cavity formation in mice. No accessory elements are needed, besides the main equipment, and it can be used in future SCI studies.

scholarly journals D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiyuan Ji ◽  
Yuxin Zhang ◽  
Chen Chen ◽  
Hui Li ◽  
Bingqiang He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signal Pathways ◽  
Post Injury ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Spinal Cord Contusion

Abstract Background Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. Methods A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. Conclusion Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

2021 ◽  
Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
External Validation ◽  
Inpatient Rehabilitation ◽  
Spinal Cord Tissue ◽  
Light Touch ◽  
Post Injury ◽  
Data Set ◽  
Cord Injury ◽  
Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

scholarly journals Obstacles and Possibilities for Participation in Sport after Spinal Cord Injury

2018 ◽  
Vol 1 (88) ◽  
Author(s):  
Kęstutis Skučas
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sport Participation ◽  
Athletic Identity ◽  
Body Part ◽  
Disabled Persons ◽  
Upper Body ◽  
Motor Disorder ◽  
Social Agents ◽  
Cord Injury

Research background and hypothesis. Studies have shown that persons after spinal cord injury rarely continue participating in sport (Stryker, Burke, 2000; Hanson, Nabavi, 2001; Stephan, Brewer, 2007). This could be caused by the obstacles that the persons face due to the motor disorder after spinal cord injury (Wu, Williams, 2001; Tasiemski et al., 2004). Hypothesis: persons with spinal cord injury while being involved in disabled sport face the same problems irrespectively of gender. Research aim was to determine the obstacles and possibilities for involvement and participation in sport after spinal cord injury.Research methods. The questionnaire method was used to collect sport participation data (Tasiemski et al., 2004) and determine socialization agents of persons after spinal cord injury (Williams, 1994). The athletic identity assessment scale (Brewer, Cornelius, 2002) was used in the research. Research results. Data showed that the majority of the subjects after spinal cord injury were not involved in sport; 11.9% did sports 1 hour per week, 13.2% – 2–3 hours per week, 10.6% – more than 6 hours per week. The value of athletic identity of paraplegic subjects was equal to 23 points, and that of tetraplegic subjects – 18 points (statistically significant data difference between the two groups when p < 0.05). It was found that athletic identity value of men after spinal cord injury (22 points) was statistically significantly higher compared to that of women (16 points, p < 0.05). Lack of adapted sport facilities – 49.6%, equipment – 53.2%, coaches – 48.4% and financial resources – 42.0% proved to be the major obstacles to participate in sport for persons after spinal cord injury.    Discussion and conclusions. According to the research, only a minority of persons after spinal cord injury identified  themselves  as  athletes.  It  was  found  that  the  main  social  agents  involving  disabled  persons  into  the mainstream of sport were other disabled persons, rehabilitation and physical therapists, coaches and other sports professionals.  Persons  after  spinal  cord  injury  believed  that  the  main  reasons  of  non-participation  in  sport  was lack  of  information  about  disabled  sport,  also  lack  of  sports  equipment,  financial  problems    and  lack  of  sports professionals. Most persons after spinal cord injury participated or would participate in sport with the aim of getting fit, strengthening the upper body part, socializing, feeling the joy of life. The majority of results of the study were similar to the results of other researchers (Tasiemski et al., 2004) who analyzed disabled persons’ problems while involving in sport.Keywords: involvement in disabled sport, athletic identity, social agents.

scholarly journals Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1697-1713 ◽  
Author(s):  
Xingxing Wang ◽  
Tianna Zhou ◽  
George D Maynard ◽  
Pramod S Terse ◽  
William B Cafferty ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Recovery Of Function ◽  
Neurological Deficits ◽  
Vehicle Group ◽  
Post Injury ◽  
Nogo Receptor ◽  
Human Dose ◽  
Cord Injury ◽  
Human Primate

Abstract After CNS trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal Nogo receptor 1 (NgR1). A soluble decoy (NgR1-Fc, AXER-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical rodent models of spinal cord injury. However, the safety and efficacy of this reagent in non-human primate spinal cord injury and its toxicological profile have not been described. Here, we provide evidence that chronic intrathecal and intravenous administration of NgR1-Fc to cynomolgus monkey and to rat are without evident toxicity at doses of 20 mg and greater every other day (≥2.0 mg/kg/day), and far greater than the projected human dose. Adult female African green monkeys underwent right C5/6 lateral hemisection with evidence of persistent disuse of the right forelimb during feeding and right hindlimb during locomotion. At 1 month post-injury, the animals were randomized to treatment with vehicle (n = 6) or 0.10–0.17 mg/kg/day of NgR1-Fc (n = 8) delivered via intrathecal lumbar catheter and osmotic minipump for 4 months. One animal was removed from the study because of surgical complications of the catheter, but no treatment-related adverse events were noted in either group. Animal behaviour was evaluated at 6–7 months post-injury, i.e. 1–2 months after treatment cessation. The use of the impaired forelimb during spontaneous feeding and the impaired hindlimb during locomotion were both significantly greater in the treatment group. Tissue collected at 7–12 months post-injury showed no significant differences in lesion size, fibrotic scar, gliosis or neuroinflammation between groups. Serotoninergic raphespinal fibres below the lesion showed no deficit, with equal density on the lesioned and intact side below the level of the injury in both groups. Corticospinal axons traced from biotin-dextran-amine injections in the left motor cortex were equally labelled across groups and reduced caudal to the injury. The NgR1-Fc group tissue exhibited a significant 2–3-fold increased corticospinal axon density in the cervical cord below the level of the injury relative to the vehicle group. The data show that NgR1-Fc does not have preclinical toxicological issues in healthy animals or safety concerns in spinal cord injury animals. Thus, it presents as a potential therapeutic for spinal cord injury with evidence for behavioural improvement and growth of injured pathways in non-human primate spinal cord injury.

An investigation into the validity and reliability of the Chinese version of Spinal Cord Independence Measure III (SCIM III)

2020 ◽  
pp. 026921552096670
Author(s):  
Huayi Xing ◽  
Nan Liu ◽  
Fin Biering-Sørensen
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Barthel Index ◽  
Pearson Correlation ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Chinese Version ◽  
Validity And Reliability ◽  
Post Injury ◽  
Cord Injury

Objective: To investigate the validity and reliability of a Chinese version of Spinal Cord Independence Measure III (SCIM III) in individuals with spinal cord injury. Design: Study on psychometric properties. Setting: An inpatient rehabilitation facility in China. Subjects: 102 participants with spinal cord injury. Mean (SD) age was 48.8 (15.6) years; tetraplegia/paraplegia ratio was 50/52; median time post injury was 2 months. Intervention: SCIM III was translated into Chinese. Chinese versions of Barthel Index and SCIM III were filled out for each participant by Rater 1. SCIM III was then administered by Rater 2 after 24 hours ( n = 67) and 7 days ( n = 65). Main Measures: Validity, inter-rater/test-retest reliability, and internal consistency of the Chinese version of SCIM III. Results: The total scores between the two raters were similar (mean ± SD: 33.8 ± 25.8 vs 33.8 ± 25.5, P = 0.95). Total agreement between the raters in each item was >80%, with both Pearson and intraclass correlation coefficients >0.97 ( P < 0.01) for each subscale and total score. The Pearson correlation coefficients of the two independent assessments performed by Rater 2 were also >0.97 ( P < 0.01) for each subscale and the total score. Cronbach α was >0.7 for each subscale and the total score for both raters. High consistency was found between Barthel Index and SCIM III total scores (Pearson correlation coefficient = 0.88, P < 0.01). Conclusion: The Chinese version of SCIM III is valid and reliable for the functional assessment of patients with SCI.

Evaluation of experimental spinal cord injury using cortical evoked potentials

1973 ◽  
Vol 39 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Stephen H. Martin ◽  
James R. Bloedel
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cortical Response ◽  
Neurological Deficits ◽  
Cystic Degeneration ◽  
Post Injury ◽  
Content Type ◽  
Cord Injury ◽  
Cortical Responses ◽  
Control Response

✓ Experiments were performed to determine if changes in cortical evoked responses could be used to predict the extent of the neurological deficits following spinal cord injury by sudden inflation of a Fogarty balloon in the epidural space cephalad to a laminectomy. The cortical responses to stimulation of the posterior tibial nerve were recorded over the sigmoid gyrus at various times following the lesion and compared with the control response. Severe, irreversible neurological deficits occurred in cats in which the cortical response either could not be evoked immediately after injury or disappeared rapidly during this period. At the end of at least 6 weeks following injury, all of these animals were paraplegic and showed severe cystic degeneration of the spinal cord. In animals in which the post-injury cortical response did not completely disappear, only mild changes were observed in a spinal cord 6 weeks following injury. This technique may be helpful in ascertaining the severity and irreversibility of a traumatic spinal cord lesion; because the technique is simple, the method may prove helpful in the clinical management of patients with spinal cord injury.

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