scholarly journals Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lan Huong Nguyen ◽  
Mingyong Gao ◽  
Junquan Lin ◽  
Wutian Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Three Dimensional ◽  
Neurological Dysfunction ◽  
Post Injury ◽  
Hydrogel Scaffold ◽  
Cord Injury ◽  
Aligned Nanofibers ◽  
Injury Treatment

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.

Paraplegia, Quadriplegia and Employment in Australia

1996 ◽  
Vol 5 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Gregory Murphy ◽  
Douglas Brown ◽  
Peter Foreman ◽  
Amanda Young ◽  
James Athanasou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Full Time ◽  
Post Injury ◽  
Employment Services ◽  
Cord Injury ◽  
Working Age ◽  
Part Time ◽  
Initial Hospital

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.

scholarly journals The Application of Omics Technologies to Study Axon Regeneration and CNS Repair

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 311 ◽  
Author(s):  
Andrea Tedeschi ◽  
Phillip G Popovich
Keyword(s):  
Spinal Cord ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
New Technologies ◽  
Axon Regeneration ◽  
Imaging Techniques ◽  
Permanent Disability ◽  
Cord Injury ◽  
Technical Advances ◽  
And Function

Traumatic brain and spinal cord injuries cause permanent disability. Although progress has been made in understanding the cellular and molecular mechanisms underlying the pathophysiological changes that affect both structure and function after injury to the brain or spinal cord, there are currently no cures for either condition. This may change with the development and application of multi-layer omics, new sophisticated bioinformatics tools, and cutting-edge imaging techniques. Already, these technical advances, when combined, are revealing an unprecedented number of novel cellular and molecular targets that could be manipulated alone or in combination to repair the injured central nervous system with precision. In this review, we highlight recent advances in applying these new technologies to the study of axon regeneration and rebuilding of injured neural circuitry. We then discuss the challenges ahead to translate results produced by these technologies into clinical application to help improve the lives of individuals who have a brain or spinal cord injury.

Three-dimensional morphometry of spinal cord injury following polyethylene glycol treatment

2002 ◽  
Vol 205 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Bradley S. Duerstock ◽  
Richard B. Borgens
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Polyethylene Glycol ◽  
Three Dimensional ◽  
Companion Paper ◽  
Behavioral Recovery ◽  
Post Injury ◽  
Cord Injury ◽  
Peg Treatment ◽  
Spinal Cord Injured

SUMMARY We are developing a novel means of restoring function after severe acute spinal cord injury. This involves a brief application of polyethylene glycol (PEG) to the site of injury. In the companion paper, we have shown that a delayed application of PEG can produce strikingly significant physiological and behavioral recovery in 90–100 % of spinal-cord-injured guinea pigs. In the present paper, we used three-dimensional computer reconstructions of PEG-treated and sham-treated spinal cords to determine whether the pathological character of a 1-month-old injury is ameliorated by application of PEG. Using a novel isocontouring algorithm, we show that immediate PEG treatment and treatment delayed by up to 7 h post-injury statistically increased the volume of intact spinal parenchyma and reduced the amount of cystic cavitation. Furthermore, in PEG-treated animals, the lesion was more focal and less diffuse throughout the damaged segment of the spinal cord, so that control cords showed a significantly extended lesion surface area. This three-dimensional computer evaluation showed that the functional recovery produced by topical application of a hydrophilic polymer is accompanied by a reduction in spinal cord damage.

scholarly journals Walking Function After Cervical Contusion and Distraction Spinal Cord Injuries in Rats

2019 ◽  
Vol 13 ◽  
pp. 117906951986961 ◽  
Author(s):  
Yue Guo ◽  
Hai Hu ◽  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Kinon Chen
Keyword(s):  
Spinal Cord ◽  
Duty Cycle ◽  
Spinal Cord Injuries ◽  
Behavioral Outcomes ◽  
Male Rats ◽  
Sprague Dawley ◽  
Post Injury ◽  
Cord Injury ◽  
Before And After ◽  
Swing Speed

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.

scholarly journals Quantification of surviving neurons after contusion, dislocation, and distraction spinal cord injuries using automated methods

2019 ◽  
Vol 13 ◽  
pp. 117906951986961
Author(s):  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Yue Guo ◽  
Hai Hu ◽  
Kinon Chen
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Morphological Characteristics ◽  
Normal Weight ◽  
Ventral Horn ◽  
Male Rats ◽  
Sprague Dawley ◽  
Post Injury ◽  
Automated Method ◽  
Cord Injury

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.

scholarly journals Activity-Based Therapy in a Community Setting for Independence, Mobility, and Sitting Balance for People With Spinal Cord Injuries

2019 ◽  
Vol 11 ◽  
pp. 117957351984162 ◽  
Author(s):  
Camila Quel de Oliveira ◽  
James W Middleton ◽  
Kathryn Refshauge ◽  
Glen M Davis
Keyword(s):  
Spinal Cord ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Spinal Cord Injuries ◽  
Spinal Injury ◽  
Post Injury ◽  
Community Based ◽  
Mixed Model Analysis ◽  
Sitting Balance ◽  
Cord Injury

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.

scholarly journals Regeneration of Corticospinal Axons into Neural Progenitor Cell Grafts After Spinal Cord Injury

2020 ◽  
Vol 15 ◽  
pp. 263310552097400
Author(s):  
Gunnar HD Poplawski ◽  
Mark H Tuszynski
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cord Injury

Spinal cord injuries leave patients with lifelong paralysis. To date, there are no therapies that promote the critical step required for the recovery of voluntary motor function: corticospinal axon regeneration. Spinal cord-derived neural progenitor cell (NPC) grafts integrate into the injured host spinal cord, enable robust corticospinal axon regeneration, and restore forelimb function following spinal cord injury in rodents. Consequently, engineered stem cell differentiation and transplantation techniques harbor promising potential for the design and implementation of therapies promoting corticospinal axon regeneration. However, in order to optimize the outcome of clinical trials, it is critical to fully understand the cellular and molecular mechanisms underlying this regeneration. Our recent study highlights the unexpected intrinsic potential of corticospinal neurons to regenerate and allows us to investigate new hypotheses exploiting this newly discovered potential.

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 ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Time Course ◽  
Spinal Cord Injuries ◽  
Molecular Level ◽  
Post Injury ◽  
Therapeutic Drugs ◽  
Cord Injury ◽  
Molecular Effects ◽  
First Time ◽  
Neurological System

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.

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