Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.

Over half of spinal cord injury (SCI) patients develop opioid-resistant chronic neuropathic pain. Safer alternatives to opioids for treatment of neuropathic pain are gabapentinoids (e.g., pregabalin and gabapentin). Clinically, gabapentinoids appear to amplify opioid effects, increasing analgesia and overdose-related adverse outcomes, but in vitro proof of this amplification and its mechanism are lacking. We previously showed that after SCI, sensitivity to opioids is reduced by fourfold to sixfold in rat sensory neurons. Here, we demonstrate that after injury, gabapentinoids restore normal sensitivity of opioid inhibition of cyclic AMP (cAMP) generation, while reducing nociceptor hyperexcitability by inhibiting voltage-gated calcium channels (VGCCs). Increasing intracellular Ca2+ or activation of L-type VGCCs (L-VGCCs) suffices to mimic SCI effects on opioid sensitivity, in a manner dependent on the activity of the Raf1 proto-oncogene, serine/threonine-protein kinase C-Raf, but independent of neuronal depolarization. Together, our results provide a mechanism for potentiation of opioid effects by gabapentinoids after injury, via reduction of calcium influx through L-VGCCs, and suggest that other inhibitors targeting these channels may similarly enhance opioid treatment of neuropathic pain.

Spinal cord injury (SCI) is a life-altering condition that severely impacts an individual\'s functional capabilities and has significant implications for both the individual and society. Large animal models are crucial for understanding the pathology and biomechanics of SCI. Dogs (Canis lupus familiaris) are promising models for SCI research due to their anatomical and histopathological similarities to humans. Balloon compression is an established method for inducing controlled SCI in canines. In this study, we optimized a balloon compression procedure for inducing SCI in dogs, aiming to develop a reliable model for future in vivo studies. Our methodology successfully induced total motoric loss in canines, observed for seven days, a critical period for therapeutic interventions. Histopathological examinations using Luxol fast blue (LFB) staining revealed total demyelination in intralesional samples, confirming the structural damage caused by balloon compression. We concluded that a balloon compression model at the T10-T11 vertebral level, with an inflated balloon volume of 1.0 ml, induced SCI while minimizing the risk of balloon rupture. Longer duration of compression ensures total paralysis in this model, providing a platform for testing therapeutic interventions during the acute phase of SCI. The canine model generated consistent data and facilitated straightforward observational findings.

MicroRNAs (miRNAs) are essential modulators of gene expression and are associated with various pathological processes, including spinal cord injury (SCI). This investigation aimed to elucidate miR-10a activity in SCI and its potential interaction with sirtuin 1 (SIRT1). The SCI rat model was established to assess hind limb movement, measure levels of miR-10a, SIRT1, neuronal survival, and inflammatory factors. An in-vitro SCI cell model was also developed to evaluate cell viability and inflammatory factor levels. The interaction between miR10a and SIRT1 was verified. Upregulated miR-10a and downregulated SIRT1 expression were found in the tissues of SCI rats. miR-10a knockdown in SCI rats enhanced the recovery of motor function, increased neuronal survival, and reduced the levels of inflammatory cytokines. Luciferase reporter assays confirmed that miR-10a targeted SIRT1 directly. In PC12 cells, downregulation of miR-10a increased SIRT1 expression, enhanced cell viability, and reduced inflammatory factor levels after LPS stimulation. Conversely, SIRT1 knockdown inhibited the protective effects of downregulated miR-10a on cell viability and inflammatory responses. The results suggest that miR-10a downregulation protects against SCI by upregulating SIRT1 expression, improving functional recovery, and reducing inflammation. Targeting the miR-10a/SIRT1 axis is a promising strategy for SCI treatment.

UNASSIGNED: Walking ability is a crucial factor for recovery and rehabilitation of spinal cord injury (SCI) patients.
UNASSIGNED: The aim of this study was to investigate the effect of 12 weeks of rebound therapy on walking parameters in SCI patients.
UNASSIGNED: Thirty members of Isfahan Spinal Cord Injury Association participated in this experimental study using a convenience sampling method. This study was approved by the ethics committee of the University of Isfahan (IR.UI.REC.1400.118). The participants were randomly assigned to control and rebound groups using a matched randomization method. Data were collected before and after 12 weeks of rebound therapy exercise (three sessions per week) in the walking laboratory, using a seven-camera 3D motion capturing system (Qualisys motion analysis). The final data were analyzed using repeated measures ANOVA in SPSS software (significance level p < .05).
UNASSIGNED: Rebound therapy training significantly improved all dependent variables (p < .05) except hip rotation, indicating its effectiveness for enhancing walking ability.
UNASSIGNED: Given the importance of walking function, we recommend the use of rebound therapy training as an exercise rehabilitation method for spinal cord injury patients.

UNASSIGNED: Respiratory complications are a leading cause of mortality post spinal cord injury (SCI). Along with breathing, respiratory muscles have a role in maintaining seated balance. Postinjury breathing influences respiratory muscle function. Preliminary evidence indicates a relation between respiratory muscle function and seated balance in people with chronic SCI dwelling in the community, but the relationship between balance and body habitus has not been explored.
UNASSIGNED: To explore the relationships among inspiratory muscle function, functional seated balance (FSB), and body habitus in people with SCI.
UNASSIGNED: A convenience sample of inpatients with SCI (C5-T12) aged 18 to 60 years who were using a wheelchair was recruited from November 2022 to March 2023. Those with additional neurological disorders or respiratory support were excluded. Respiratory muscle function measures included maximal inspiratory pressure (MIP), sustained MIP (SMIP), and Fatigue Index Test (FIT). FSB was scored using the Function in Sitting Test (FIST). Body habitus was assessed using the axillary: umbilical (A:U) ratio. Spearman correlations explored the relationships.
UNASSIGNED: Thirty-eight of 42 screened participants were eligible and participated (male, 32). Levels of injury ranged from C5 to T12. The mean (SD) age and duration of injury of the sample was 25.61 (6.68) years and 31.03 (28.69) months, respectively. SMIP and FIT correlated significantly with FSB (r s= .441, p = .01, and r s= .434, p = .006, respectively). A significant correlation between SMIP and A:U ratio (r s= -.330, p = .043) was observed.
UNASSIGNED: We observed a significant correlation between inspiratory pressure parameters and both functional seated balance and body habitus, adding to evidence on postural role of respiratory muscles.

This paper provides an overview of the history, composition, organization, responsibilities, and regulatory requirements of Data Safety Monitoring Boards (DSMB), with particular reference to the context of clinical trials in spinal cord injury. It is intended to help potential members of such boards and those undertaking the design of new clinical trials to understand the important role of the DSMB in safeguarding the integrity of complex trials, promoting safety, and countering potential bias. An independent DSMB helps to protect research subjects by providing study oversight and serves as an additional step to assure that clinical trials are performed to existing and appropriate standards. The DSMB must meet on a regular schedule, diligently evaluate all the information it receives, and report in a timely and decisive manner. Members must be free of significant conflicts of interest throughout the study and be adequately trained and experienced to serve their roles within the group. DSMB service can be a valuable learning experience and a gratifying opportunity to participate in advancing medicine and helping to maintain and improve the standards of research.

UNASSIGNED: The inclusion of people living with spinal cord injury (SCI) in research has allowed for an informed understanding of priorities of recovery of which bowel dysfunction and bladder dysfunction have been continuously identified. Research has also demonstrated the global disparities in SCI outcomes particularly when comparing high- and low-income countries. Currently, there is a lack of direct comparison between countries when assessing SCI outcomes.
UNASSIGNED: This is an exploratory study to better understand bowel and bladder dysfunction amongst individuals with SCI in India and Canada.
UNASSIGNED: Data from 33 participants were analyzed. Participants completed an online questionnaire assessing demographic information and the Neurogenic Bowel Dysfunction (NBD) score, Wexner score, Neurogenic Bladder Symptom Score (NBSS), and the Incontinence Quality of Life Instrument (I-QOL). Continuous data were compared using t tests. For not normally distributed data, the independent Mann-Whitney U test was used. Categorical variables were evaluated for association using Fisher\'s exact or chi-square test, depending on the sample size.
UNASSIGNED: Independent Mann-Whitney U test demonstrated that the Canadian participants had poorer bowel function with higher total NBD scores (p = .007) and less frequent bowel movements (p = .036), and they were more likely to experience uneasiness, headaches, and perspiration during bowel movements (p < .001). NBSS results indicated a small but significantly higher proportion of the Indian participants were unsatisfied or unhappy with their bladder function (p = .049). The distribution of Wexner and I-QOL scores were the same across countries.
UNASSIGNED: Potential explanations for differences include lifestyle, management, financial resources, patient and caregiver education, and societal pressures, which are all heavily influenced by cultural, geographical, and economic circumstances.

UNASSIGNED: The proportion of patients with American Spinal Injury Association Impairment Scale (AIS) grade D traumatic spinal cord injuries (tSCI) is increasing. Although initial motor deficits can be relatively mild, some individuals fail to recover functional independence.
UNASSIGNED: This study aims to identify factors associated with failure to reach complete functional independence after AIS grade D tSCI.
UNASSIGNED: An observational prospective cohort study was conducted at a level 1 trauma center specialized in SCI care. A prospective cohort of 121 individuals with an AIS-D tSCI was considered. The baseline characteristics, length of acute stay, need for inpatient rehabilitation, and 12-month functional status were assessed. Univariate and classification and regression tree (CART) analyses were performed to identify factors associated with reaching complete versus incomplete functional independence (defined as perfect total SCIM III score at 12-month follow-up).
UNASSIGNED: There were 69.3%, 83.3%, and 61.4% individuals reaching complete independence in self-care, respiration/sphincter management, and mobility, respectively. A total of 64 individuals (52%) reached complete functional independence in all three domains. In the CART analysis, we found that patients are more likely to achieve complete functional independence when they have a baseline motor score ≥83 (65% individuals) and if they present fewer medical comorbidities (70% individuals if Charlson Comorbidity Index [CCI] ≤4).
UNASSIGNED: About half of individuals with AIS grade D tSCI can expect complete long-term functional independence. It is important to recognize early during acute care individuals with baseline motor score <83 or a high burden of comorbidities (CCI ≥5) to optimize their rehabilitation plan.

UNASSIGNED: Guidelines fail to recommend objective measures to assist with treatment of neurogenic bowel dysfunction (NBD) in spinal cord injury (SCI).
UNASSIGNED: The main objective was to review the literature to identify the objective measures used in all NBD populations and to present their results and any correlations performed to validated subjective measures.
UNASSIGNED: A systematic review of the literature was performed in accordance with PRISMA (2020) guidelines, including all records from January 2012 to May 2023 with MeSH terms like \"neurogenic bowel\" indexed in the following databases: PubMed, EMBASE, CINAHL, Cochrane Central Trials Register, and ClinicalTrials.gov. Abstracts were excluded if they did not include objective measures or if they only mentioned the esophagus, stomach, and/or small bowel. Records were screened independently by at least two collaborators, and differences were resolved by unanimous agreement.
UNASSIGNED: There were 1290 records identified pertaining to NBD. After duplicates were removed, the remaining records were screened for a total of 49 records. Forty-one records (82%) included subjective measures. Two-thirds of the articles involved the population with SCI/disease (n = 552) and one-third were non-SCI NBD (n = 476). Objective measures were categorized as (1) transit time, (2) anorectal physiology testing, and (3) miscellaneous. Of the 38 articles presenting results, only 16 (42%) performed correlations of objective measures to subjective measures.
UNASSIGNED: There is an abundance of literature supporting the use of objective outcome measures for NBD in SCI. Strong correlations of subjective measures to objective outcome measures were generally lacking, supporting the need to use both measures to help with NBD management.