scholarly journals Exerting the Appropriate Application of Methylprednisolone in Acute Spinal Cord Injury Based on Time Course Transcriptomics Analysis

2021 ◽  
Vol 22 (23) ◽  
pp. 13024
Author(s):  
Liang-Yo Yang ◽  
Meng-Yu Tsai ◽  
Shu-Hui Juan ◽  
Shwu-Fen Chang ◽  
Chang-Tze Ricky Yu ◽  
...  

Methylprednisolone (MP) is an anti-inflammatory drug approved for the treatment of acute spinal cord injuries (SCIs). However, MP administration for SCIs has become a controversial issue while the molecular effects of MP remain unexplored to date. Therefore, delineating the benefits and side effects of MP and determining what MP cannot cure in SCIs at the molecular level are urgent issues. Here, genomic profiles of the spinal cord in rats with and without injury insults, and those with and without MP treatment, were generated at 0, 2, 4, 6, 8, 12, 24, and 48 h post-injury. A comprehensive analysis was applied to obtain three distinct classes: side effect of MP (SEMP), competence of MP (CPMP), and incapability of MP (ICMP). Functional analysis using these genes suggested that MP exerts its greatest effect at 8~12 h, and the CPMP was reflected in the immune response, while SEMP suggested aspects of metabolism, such as glycolysis, and ICMP was on neurological system processes in acute SCIs. For the first time, we are able to precisely reveal responsive functions of MP in SCIs at the molecular level and provide useful solutions to avoid complications of MP in SCIs before better therapeutic drugs are available.

Author(s):  
A Galuta ◽  
A Yassin Kassab ◽  
D Ghinda ◽  
R Sandarage ◽  
J Kwan ◽  
...  

Background: While the use of neural stem/progenitor cells has been reported as a promising therapeutic approach for spinal cord injury, direct comparison of adult primary animal spinal cord NSPCs have not been compared to human NSPCs under the same conditions to characterize intrinsic differences between human/animal NSPC response to inflammatory/regenerative factors. Methods: To mimic post-injury inflammation, primary-derived NSPCs from adult humans, pigs, and rats were treated with pro-inflammatory factors.To direct regeneration, NSPCs were treated with retinoic acid, platelet-derived growth factor or bone morphogenic protein-(BMP4) to induce neurons, oligodendrocytes or astrocytes, respectively.Cultures were treated for 7 or 14 days and characterized by immunocytochemistry. Results: Pro-inflammatory factors promoted more astrogenesis in rat and pig NSPCs compared to human NSPCs and induced neuronal differentiation in human NSPCs. RA increased neurogenesis of human and rat NSPCs, PDGFα increased oligodendrocyte differentiation of rat NSPCs, and BMP4 increased astrogenesis of human and rat NSPCs Conclusions: For the first time, differences in response of human, pig and rat primary NSPCs to inflammatory and regenerative factors have been identified. Better understanding of these differences is essential to improving the successful translation of regenerative therapies to humans.


1996 ◽  
Vol 5 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Gregory Murphy ◽  
Douglas Brown ◽  
Peter Foreman ◽  
Amanda Young ◽  
James Athanasou

The educational and vocational achievements of a sample of Australians with spinal cord injuries are described in this study. Of the 180 working-age people surveyed, 36% were holding full-time or part-time employment at the time of the survey and one-third had gone on to obtain further qualifications post-injury. The most frequent methods of finding a job post-injury were informal rather than formal, with only 5% of jobs gained through advertisements or employment services. Of those who gained work, 49% did so within 12 months of discharge, but another 14% obtained their job more than five years after initial hospital discharge. The results indicate that there is considerable scope for employment and education achievements following spinal cord injury.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lan Huong Nguyen ◽  
Mingyong Gao ◽  
Junquan Lin ◽  
Wutian Wu ◽  
Jun Wang ◽  
...  

Abstract Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications.


2020 ◽  
Vol 203 ◽  
pp. e535-e536
Author(s):  
Tetsuichi Saito* ◽  
Masahiro Kurobe ◽  
Daisuke Gotoh ◽  
Taro Igarashi ◽  
Osamu Ishizuka ◽  
...  

2019 ◽  
Vol 13 ◽  
pp. 117906951986961 ◽  
Author(s):  
Yue Guo ◽  
Hai Hu ◽  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Kinon Chen

This study examines and compares the walking function in contusion and distraction spinal cord injury (SCI) mechanisms. Moderate contusion and distraction SCIs were surgically induced between C5 and C6 in Sprague-Dawley male rats. The CatWalk system was used to perform gait analysis of walkway walking. The ladder rung walking test was used to quantify skilled locomotor movements of ladder rung walking. It was found that the inter-paw coordination, paw support, front paw kinematics, hind paw kinematics, and skilled movements were significantly different before and after contusion and distraction. Step sequence duration, diagonal support, forelimb intensity, forelimb duty cycle, forelimb paw angle, and forelimb swing speed were more greatly affected in distraction than in contusion at 2 weeks post-injury, whereas hindlimb stand was more greatly affected in contusion than in distraction at 8 weeks post-injury. After 8 weeks post-injury, diagonal coupling—variation, girdle coupling—variation, ipsilateral coupling—mean, forelimb maximum contact at, forelimb intensity, forelimb paw angle, and number of forelimb misplacements recovered to normal in contusion but not in distraction, whereas step sequence duration, ipsilateral coupling—variation, forelimb stand, forelimb duty cycle, hindlimb swing duration, hindlimb swing speed, and number of forelimb slips recovered to normal in distraction but not in contusion. Some of the behavioral outcomes, but not the others, were linearly correlated with the histological outcomes. In conclusion, walking deficits and recovery can be affected by the type of common traumatic SCI.


2019 ◽  
Vol 13 ◽  
pp. 117906951986961
Author(s):  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Yue Guo ◽  
Hai Hu ◽  
Kinon Chen

This study proposes and validates an automated method for counting neurons in spinal cord injury (SCI) and then uses it to examine and compare the surviving cells in common types of SCI mechanisms. Moderate contusion, dislocation, and distraction SCIs were surgically induced in Sprague Dawley male rats (n = 6 for each type of injury). Their spinal cords were harvested 8 weeks post injury with 5 normal weight-matched rats. The spinal cords were cut, stained with anti-NeuN antibody and fluorescent Nissl, and imaged in the dorsal and ventral horns at various distances to the epicenter. Neurons in the images were automatically counted using an algorithm that was designed to filter non-soma-like objects based on morphological characteristics (size, solidity, circular pattern) and check the remaining objects for the double-stained nucleus/cell body features (brightness variation, brightness distribution, color). To validate the automated method, some of the images were randomly selected for manual counting. The number of surviving cells that were automatically measured by the algorithm was found to be correlated with the values that were manually measured by 2 observers ( P < .001) with similar differences ( P > .05). Neurons in the dorsal and ventral horns were reduced after the SCIs ( P < .05). Dislocation and distraction, respectively, caused the most severe damage to the ventral horn neurons especially near the epicenter and the most extensive and uniform damage to the dorsal horn neurons ( P < .05). Our method was proved to be reliable, which is suitable for studying different types of SCI.


Author(s):  
Rukhulla Zabikhullaevich Khikmatullaev ◽  
Alisher Iskandarovich Iskandarov ◽  
Dildora Zabikhullaevna Khakimova

Objective: to analyze main clinical-statistical indices of spine and spinal cord injuries (SCI) and system of organization of medical aid to the victims. We conducted a cohort retrospective study of materials of medical institutions of Tashkent city. Medical records of patients and records of forensic examinations were analyzed. 242 cases of spinal cord injuries were studied. Over the last 10 years in Tashkent the frequency of SCI have been tend to increase, males and working-age people are dominated. In 60.9% of cases the injury was associated, in 36.2% - isolated, and in 2.9% - combined. Fallings from height and road traffic accidents were the main reasons for getting SCI. Lesions at cervical level registered in 45% of cases, thoracic level - 27.3%, at lumbar level - 27.7%, respectively. According to ASIA/IMSOP, full injuries were noted in 40.1% of cases, incomplete injures were in 59.9%. Overall mortality from SCI was 68.6%. Thus, for the first time this study allowed to get in detail the clinical and statistical indicators of SCI in the region.


2019 ◽  
Vol 11 ◽  
pp. 117957351984162 ◽  
Author(s):  
Camila Quel de Oliveira ◽  
James W Middleton ◽  
Kathryn Refshauge ◽  
Glen M Davis

Introduction: Activity-based therapy (ABT) aims to activate the neuromuscular system below the level of the spinal cord lesion and promote recovery of motor tasks through spinal reorganisation, motor learning and changes to muscles and sensory system. We investigated the effects of a multimodal ABT program on mobility, independence and sitting balance in individuals with spinal cord injury (SCI). Methods: Retrospective clinical data from 91 adults who independently enrolled in four community-based ABT centres in Australia were analysed. The multimodal ABT program was delivered for 3 to 12 months, one to four times per week. Assessments were undertaken every 3 months and included the Modified Rivermead Mobility Index (MRMI), Spinal Cord Independence Measure (SCIM) and seated reach distance (SRD). A linear mixed model analysis was used to determine time-based and other predictors of change. Results: There was a significant improvement after 12 months for all outcome measures, with a mean change score of 4 points in the SCIM (95% confidence interval [CI]: 2.7-5.3, d = 0.19), 2 points in the MRMI (95% CI: 1-2.3, d = 0.19) and 0.2 in the SRD (95% CI: 0.1-2.2, d = 0.52). Greater improvements occurred in the first 3 months of intervention. There were no interaction effects between time and the neurological level of injury, American Spinal Injury Association Impairment Scale classification, or duration post-injury for most outcomes. Conclusions: A community-based ABT exercise program for people with SCI can lead to small improvements in mobility, independence and balance in sitting, with greater improvements occurring early during intervention.


2018 ◽  
Vol 9 (5) ◽  
pp. 545-558 ◽  
Author(s):  
Julio C. Furlan ◽  
Sivakumar Gulasingam ◽  
B. Catharine Craven

Study Design: Systematic review. Objectives: War-related spinal cord injuries (SCIs) are commonly more severe and complex than traumatic SCIs among civilians. This systematic review, for the first time, synthesized and critically appraised the literature on the epidemiology of war-related SCIs. This review aimed to identify distinct features from the civilian SCIs that can have an impact on the management of military and civilian SCIs. Methods: Medline, EMBASE, and PsycINFO databases were searched for articles on epidemiology of war-related SCI among combatants, published from 1946 to December 20, 2017. This review included only original publications on epidemiological aspects of SCIs that occur during an act of war. The STROBE statement was used to examine the quality of the publications. Results: The literature search identified 1594 publications, of which 25 articles fulfilled the inclusion and exclusion criteria. The studies were classified into the following topics: 17 articles reported demographics, level and severity of SCI, mechanism of injury and/or associated bodily injuries; 5 articles reported the incidence of war-related SCI; and 6 articles reported the frequency of SCI among other war-related bodily injuries. Overall, military personnel with war-related SCI were typically young, white men, with predominantly thoracic or lumbar level, complete (American Spinal Injury Association [ASIA] Impairment Scale A) SCI due to gunshot or explosion and often associated with other bodily injuries. Marines appear to be at a greater risk of war-related SCI than the military personal in the Army, Navy, and Air Force. Conclusions: The war-related SCIs among soldiers are distinct from the traumatic SCI in the general population. The majority of the current literature is based on the American experiences in most recent wars.


2021 ◽  
Vol 22 (4) ◽  
pp. 1744
Author(s):  
Andrea Bighinati ◽  
Zahra Khalajzeyqami ◽  
Vito Antonio Baldassarro ◽  
Luca Lorenzini ◽  
Maura Cescatti ◽  
...  

The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the “core” area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.


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