Spinal Cord Injury Research Research Articles

A bipedal mammalian model for spinal cord injury research: The tammar wallaby

Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropus eugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7–60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.

A bipedal mammalian model for spinal cord injury research: The tammar wallaby.

Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropuseugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7-60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.

Research progress from the SCI Model Systems (SCIMS): An interactive discussion on future directions

Context/Objective: To describe current and future directions in spinal cord injury (SCI) research.Design: The SCI Model Systems (SCIMS) programs funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) during the 2011 to 2016 cycle provided abstracts describing findings from current research projects. Discussion among session participants generated ideas for research opportunities.Setting/Participants: Pre-conference workshop before the 2016 American Spinal Injury Association (ASIA) annual meeting. A steering committee selected by the SCIMS directors that included the moderators of the sessions at the ASIA pre-conference workshop, researchers presenting abstracts during the session, and the audience of over 100 attending participants in the pre-conference workshop.Methods/Results: Group discussion followed presentations in 5 thematic areas of (1) Demographics and Measurement; (2) Functional Training; (3) Psychosocial Considerations; (4) Assistive Technology; and (5) Secondary Conditions. The steering committee reviewed and summarized discussion points on future directions for research and made recommendations for research based on the discussion in each of the five areas.Conclusion: Significant areas in need of research in SCI remain, the goal of which is continued improvement in the quality of life of individuals with SCI.

Targeting Translational Successes through CANSORT-SCI: Using Pet Dogs To Identify Effective Treatments for Spinal Cord Injury.

Translation of therapeutic interventions for spinal cord injury (SCI) from laboratory to clinic has been historically challenging, highlighting the need for robust models of injury that more closely mirror the human condition. The high prevalence of acute, naturally occurring SCI in pet dogs provides a unique opportunity to evaluate expeditiously promising interventions in a population of animals that receive diagnoses and treatment clinically in a manner similar to persons with SCI, while adhering to National Institutes of Health guidelines for scientific rigor and transparent reporting. In addition, pet dogs with chronic paralysis are often maintained long-term by their owners, offering a similarly unique population for study of chronic SCI. Despite this, only a small number of studies have used the clinical dog model of SCI. The Canine Spinal Cord Injury Consortium (CANSORT-SCI) was recently established by a group of veterinarians and basic science researchers to promote the value of the canine clinical model of SCI. The CANSORT-SCI group held an inaugural meeting November 20 and 21, 2015 to evaluate opportunities and challenges to the use of pet dogs in SCI research. Key challenges identified included lack of familiarity with the model among nonveterinary scientists and questions about how and where in the translational process the canine clinical model would be most valuable. In light of these, we review the natural history, outcome, and available assessment tools associated with canine clinical SCI with emphasis on their relevance to human SCI and the translational process.

Localization of the corticospinal tract within the porcine spinal cord: Implications for experimental modeling of traumatic spinal cord injury

Spinal cord injury (SCI) researchers have predominately utilized rodents for SCI modeling and experimentation. Unfortunately, a large number of novel therapies developed in rodent models have failed to demonstrate efficacy in human clinical trials which suggests that improved animal models are an important translational tool. Recently, porcine models of SCI have been identified as a valuable intermediary model for preclinical evaluation of promising therapies to aid clinical translation. However, the localization of the major spinal tracts in pigs has not yet been described. Given that significant differences exist in the location of the corticospinal tract (CST) between rodents and humans, determining its location in pigs will provide important information related to the translational potential of the porcine pre-clinical model of SCI. Thus, the goal of this study is to investigate the localization of the CST within the porcine spinal cord. Mature female domestic pigs (n=4, 60kg) received microinjections of fluorescent dextran tracers (Alexa Fluor, 10,000MW) into the primary motor cortex, using image-guided navigation (StealthStation®), to label the CST. At 5 weeks post-tracer injection animals were euthanized, the entire neuroaxis harvested and processed for histological examination. Serial sections of the brain and spinal cord were prepared and imaged using confocal microscopy to observe the location of the CST in pigs. Results demonstrate that the CST of pigs is located in the lateral white matter, signifying greater similarity to human anatomical structure compared to that of rodents. We conclude that the corticospinal tract in pigs demonstrates anatomical similarity to human, suggesting that the porcine model has importance as a translational intermediary pre-clinical model.

Burden of care in primary caregivers of individuals with spinal cord injury in Iran: its association with sociodemographic factors.

A descriptive cross-sectional study. The burden of care among primary caregivers of individuals with spinal cord injury (SCI) is affected by different factors. We aimed to evaluate the level of burden among caregivers and the association between the caregiver burden and sociodemographic factors of SCI individuals and their caregivers. Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. The Zarit caregiver burden interview was used to evaluate the level of burden in caregivers through structured face-to-face interviews with 163 individuals with SCI, who were referred to receive outpatient rehabilitation, and their caregivers. The mean of caregivers' burden score was 38.9±15.2 and 11.7% reported no or little burden, 43.6% reported 'mild-to-moderate' burden, 33.1% reported 'moderate-to-severe' burden and 11.7% reported 'severe' burden of care. There was relationship between the level of injury (P=0.010) and occupational status (P=0.041) in SCI individuals and caregiver burden score. There was also a positive relationship between the caregiver burden score and duration of injury (r=0.176, P=0.025), the caregivers' age (r=0.350, P<0.001), and length of time that the current caregiver providing care (r=0.253, P=0.001). There was a negative relationship between the burden and caregiver's educational level (r=-0.235, P=0.002). The burden of care among the caregivers of SCI individuals is a multidimensional issue. The sociodemographic characteristics of individuals with SCI and their caregivers can affect the caregiver's burden. Many of these factors can be modified to reduce the burden of care.

How Do Iranian People with Spinal Cord Injury Understand Marriage?

Background: Spinal cord injury (SCI) is a life-altering experience. There is little information about the perspectives of people with SCI toward marriage. Purpose: To explore the understandings of Iranian adults with SCI about marriage. Methods: In this qualitative inquiry, using a semi-structured interview guide, we collected data from 53 single adults with SCI (41 men and 12 women) who were referred to the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences in Tehran. Barun and Clarke's thematic analysis approach was applied for data analysis. Results: "Marriage" was thematized in outer and inner scenarios. The outer scenario was explored in terms of physical disability identified as a seminal determinant in successful marriage. "Attractiveness," "able body for breadwinning," "sexually active," and "reproduction" were dominant concepts extracted from the participants' narratives. The participants' inner scenarios revealed that marriage would be welcomed if a potential partner accepted them as a "whole person" regardless of their SCI condition. Conclusion: The findings suggest that adults with SCI do not ignore or reject marriage, however it was not their life priority due to major concerns that they had internalized. Considering the quality of care, people with SCI must be reassured about their potential to get married. SCI-based sexuality education and premarital counseling support the patients in their postmarital lives. Our findings will provide decision makers and health providers with significant insight for utilizing culturally appropriate services for people with SCI.

The translational importance of establishing biomarkers of human spinal cord injury

The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging. Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable. Furthermore, the difficulty in predicting neurologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power. Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research. As such, the objective of the present review was to describe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood. We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neurological outcome.

From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

Association of pain, social support and socioeconomic indicators in patients with spinal cord injury in Iran.

Descriptive cross-sectional study. Pain is a prevalent complication of individuals with spinal cord injury (SCI). Our objective was to examine the association between social support, socioeconomic factors and psychosocial factors and pain to develop more effective management strategies. Brain and Spinal Cord Injury Research (BASIR) Center, Tehran University of Medical Sciences, Tehran, Iran. The Persian version of the Brief Pain Inventory was used to measure the pain, and the Multidimensional Scale of Perceived Social Support was used to measure social support through structured face-to-face interviews in SCI individuals. The overall prevalence of pain was 50.7%; 79.3% of individuals had bilateral pain, with lower limbs and back being the most common location. The quality of pain was described as aching (41.4%), tingling (32.9%), pressure (15.7%), coldness (5.7%) and feeling electric shock sensations (4.3%). The frequency of pain in individuals with paraplegia (60.9% vs 45.7%) and incomplete (53.5% vs 52.5%) SCI was higher than with other types of neurological injuries. Patients with a medium level of education had the least pain and those with good economic situation reported higher frequency of having pain (P=0.034). There was no significant relationship between pain and social support. There was a positive correlation between pain and impairment of mood, normal work, relations with other people and lack of sleep (P<0.001). These novel findings will inform the development of strategies to manage pain by improving access to health-care facilities and supplies.

Rat models of spinal cord injury: from pathology to potential therapies.

ABSTRACTA long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.

An omic approach to spinal cord injury mechanisms

Spinal cord injury (SCI) research continues to make substantial progress in identifying both neuron-intrinsic and neuron-extrinsic mechanisms that limit central nervous system (CNS) plasticity and regeneration

The effect of behavioral intervention and nutrition education program on serum lipid profile, body weight and blood pressure in Iranian individuals with spinal cord injury: A randomized clinical trial

Objective: The efficacy of nutrition education on body weight and serum lipids has not yet been described in patients with spinal cord injury (SCI). In the present study, we examined the effect of a 7-month nutrition education program on lipid profile and body weight in individuals with SCI.Design: Randomized clinical trial.Setting: A tertiary rehabilitation center.Participants: Patients with SCI who were referred to Brain and Spinal Cord Injury Research Center.Intervention: The nutrition education program consisted of 5 education sessions during a period of 7 months.Outcome measures: Body weight and serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measure at the beginning of the trial and after 7 months. Two-way repeated measure analysis of variance (ANOVA) was used.Results: Total of 57 patients (27 in control group and 30 in education group) participated. Nutrition education program showed no significant effect on the levels of TC, TG, LDL-C and HDL-C (P: 0.224, 0.172, 0.107 and 0.081, respectively). No significant changes in weight and waist circumflex have been observed as well (P: 0.970 and 0.361, respectively).Conclusion: Our findings do not support a significant influence of nutrition education program on weight and lipid profile. It seems that the nutrition education program alone is not adequately effective to have beneficial influence on weight and lipid profile.Clinical trial registration No.: IRCT201406215968N3

Translational Relevance of Swine Models of Spinal Cord Injury.

Spinal cord injury (SCI) is a physically and psychologically devastating clinical condition. The typical treatment regimens of decompressive surgery and rehabilitation therapy still leave many patients with permanent disability. The development of new therapies and devices can be accelerated if relevant translational animal models are more effectively used in pre-clinical stages. Swine is a highly relevant model for SCI research, especially with respect to spine and spinal cord anatomy, spine vasculature, immune responses to injury, and functional assessments. Several spine injury models have recently been developed for swine and are beginning to be used to evaluate new therapies. Swine models of SCI offer tremendous advantages for efficient translation of pre-clinical discoveries and the development of new therapies and devices. Future swine models will also be enhanced by advances in gene-editing technology to further elucidate the complex pathophysiology associated with SCI and provide a means to engineer specific spinal pathologies.

Standardization of Data for Clinical Use and Research in Spinal Cord Injury.

Increased survival after spinal cord injury (SCI) worldwide has enhanced the need for quality data that can be compared and shared between centers, countries, as well as across research studies, to better understand how best to prevent and treat SCI. Such data should be standardized and be able to be uniformly collected at any SCI center or within any SCI study. Standardization will make it possible to collect information from larger SCI populations for multi-center research studies. With this aim, the international SCI community has obtained consensus regarding the best available data and measures for use in SCI clinical practice and research. Reporting of SCI data is likewise standardized. Data elements are continuously updated and developed using an open and transparent process. There are ongoing internal, as well as external review processes, where all interested parties are encouraged to participate. The purpose of this review paper is to provide an overview of the initiatives to standardize data including the International Spinal Cord Society’s International SCI Data Sets and the National Institutes of Health, National Institute of Neurological Disorders and Stroke Common Data Elements Project within SCI and discuss future opportunities.

Reexamining the Validity and Dimensionality of the Moorong Self-Efficacy Scale: Improving Its Clinical Utility

ObjectiveTo improve the clinical utility of the Moorong Self-Efficacy Scale (MSES) by reexamining its factor structure and comparing its performance against a measure of general self-efficacy in persons with spinal cord injury (SCI). DesignCross-sectional survey design. SettingCommunity. ParticipantsAdults with SCI (N=161; 118 men and 43 women) recruited from Australia (n=82) and the United States (n=79), including 86 with paraplegia and 75 with tetraplegia. InterventionsNone. Main Outcome MeasuresConfirmatory factor analysis deriving fit indices on reported 1-, 2-, and 3-factor structures for the MSES. Exploratory factor analysis of MSES using principal component analysis with promax oblique rotation and structure validation, with correlations and multiple regression using cross-sectional data from the Sherer General Self-Efficacy Scale and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). ResultsThe MSES was confirmed to have a 3-factor structure, explaining 61% of variance. Two of the factors, labeled social function self-efficacy and personal function self-efficacy, were SCI condition–specific, whereas the other factor (accounting for 9.7% of variance) represented general self-efficacy, correlating most strongly with the Sherer General Self-Efficacy Scale. Correlations and multiple regression analyses between MSES factors, Sherer General Self-Efficacy Scale total score, SF-36 Physical and Mental Component Summary scores, and SF-36 domain scores support validity of this MSES factor structure. No significant cross-cultural differences existed between Australia and the United States in total MSES or factor scores. ConclusionsThe findings support a 3-factor structure encompassing general and SCI domain–specific self-efficacy beliefs and better position the MSES to assist SCI rehabilitation assessment, planning, and research.

Spinal cord injury and women's sexual life: case-control study.

The objective of this study was to estimate the magnitude of association between spinal cord injury (SCI) and women's quality of sexual life and sexual function. This study was conducted in the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. From the referral university-based clinics, we used simple random sampling to recruit 62 women: 31 women with SCI and 31 women without SCI. Socio-demographic and reproductive traits questionnaire, Sexual Quality of life-Female (SQOL-F), Female Sexual Function Index (FSFI) and Spinal Cord Independence Measure (SCIM) were completed using telephone and face-to-face interviews in the cases and controls. After univariate analyses, multivariate linear and proportional odds regression models were conducted to investigate the relation between SCI and women's quality of sexual life, as well as sexual function. The mean age of cases and controls was 35.42±6.51 and 33.77±4.02 years. Most women were high school-educated and housewives. Adjusting for probable confounders, the proportional odds regression model showed a significant relationship between the spinal cord injury (AOR=4.2, 95% CI: 1.8-9.2), non-college-educated (AOR=3.1, 95% CI: 1.2-5.9) and employed (AOR=1.8, 95% CI: 1.1-1.8) variables and being in one of the moderate or poor quality of life classes. Scores of SQOL-F and FSFI domains, except satisfaction, were significantly worse in cases versus controls (P<0.001). Although our participants showed low sexual dysfunction, they tended to report moderate to poor quality of sexual life. Our findings support the implication that sexual rehabilitation must be provided for women with SCI soon after injury.

Correlative Microscopy Application in Spinal Cord Injury Research

Correlative Microscopy Application in Spinal Cord Injury Research

Spinal cord injury: a review of the most-cited publications.

The objective of this study was to identify and review the most-cited articles on spinal cord injury (SCI). Citation analyses showcase the relative influence of individual articles in a given field. In addition to distinguishing publications of particular quality and impact and well-developed areas of the literature, citation analyses allow for an understanding of the direction in which a field of research is headed. A multi-disciplinary bibliographic index was used to identify the 50 SCI articles with the most lifetime citations, and the 50 SCI articles with the highest annual citation rates. Studies were categorized into one of six categories based on their primary focus: treatment, pathology/natural history, predictor of outcome, methods, epidemiology, or assessment measure. We report that 40.0 and 56.0% of SCI papers with the most lifetime citations and highest annual citation rates, respectively, were systematic reviews or meta-analyses, indicating that some of the most referenced papers in SCI are not primary publications. Further, there appears to be a greater international presence in SCI research. In the highest annual citation rate cohort, 14.0% of papers were a product of international collaboration, 50.0% were published by outside of the United States, and the average year of publication was 2005±5.4; the comparable numbers for papers that comprised the highest lifetime citation cohort were, respectively, 8.0, 28.0%, and 1998±9.2. Treatment and pathology/natural history of SCI were a common research focus in both citation cohorts, consistent with ongoing efforts to better understand and manage this injury. This comprehensive review provides a cross-sectional summary and bibliometric analysis of some of the most influential literature in SCI, and compliments existing systematic reviews and meta-analysis in the field by establishing which areas of the literature are growing and which have been well developed.

Harmonization of Databases: A Step for Advancing the Knowledge About Spinal Cord Injury

The objectives of this article are to (1) provide an overview of existing spinal cord injury (SCI) clinical research databases—their purposes, characteristics, and accessibility to users; and (2) present a vision for future collaborations required for cross-cutting research in SCI. This vision highlights the need for validated and relevant data for longitudinal clinical trials and observational and epidemiologic SCI-related studies. Three existing SCI clinical research databases/registries are reviewed and summarized with regard to current formats, collection methods, and uses, including major strengths and weaknesses. Efforts to provide a uniform approach to data collection are also reviewed. The databases reviewed offer different approaches to capture important clinical information on SCI. They vary on size, purpose, data points, inclusion of standard outcomes, and technical requirements. Each presents with a set of limitations including lack of population data and lack of a common platform for data comparisons and exchanges. It is clear that numerous issues need to be considered when planning to establish common ways of collecting data through data sets or patient registries, ranging from a carefully crafted implementation plan that lists purposes, cost, resources required, and policies to guide such development to establishing a framework for dissemination of data and findings. For the present, taking advantage of the vast but different data already collected over many decades may require a variety of statistical skills and epidemiologic techniques. Ultimately, our ability to speak the same language with regard to variables and assessment tools will facilitate international collaborations and enhance comparability, data pooling, and the ability to generalize findings to a broader population.