Spinal Cord Injury Model Research Articles

Regenerative medicine for spinal cord injury using induced pluripotent stem cells: from animals to humans

Abstract Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated.

Therapeutic potential of EVs loaded with CB2 receptor agonist in spinal cord injury via the Nrf2/HO-1 pathway

ABSTRACT Background Spinal cord injury (SCI) poses a challenge due to limited treatment options. Recently, the effect and mechanism of Exo-loaded cannabinoid receptor type 2 (CB2) agonist AM1241(Exo + AM1241) have been applied in other inflammatory diseases but not in SCI. Methods The SCI model was set up using C57BL/6 mice, followed by the treatment of Exo, AM1241, and Exo + AM1241. We assessed the effects of the following treatments on motor function recovery using BMS, and evaluated histological changes, apoptosis activity, inflammation, and oxidative stress in the SCI mice model. Additionally, the effect of following treatments on spinal cord neural stem cells (NSCs) was evaluated under lipopolysaccharides (LPS) induced inflammatory and oxidative models and, glutamate (Gluts) induced cell apoptosis models. Result Our results demonstrated that Exo + AM1241 treatment significantly improved motor function recovery, after SCI by decreasing proinflammatory cytokines, and suppressing astrocyte/microglia (GFAP/Iba1) activation in the injury zone. Additionally, this treatment reduces pro-apoptotic proteins (Bax and caspase 3), increases the levels of the anti-apoptotic protein Bcl-2, enhances antioxidant defenses by boosting SOD and GSH, and lowers oxidative stress markers such as MDA. It also activates the Nuclear factor erythroid-2 (Nrf2) related factor 2 signaling pathway, thereby enhancing tissue protection against damage and cell death.

Fish Species Spinal Cord Injury Models Utility for Research: A Systematic Review of Methodologies and Outcomes

Context: Spinal cord injury (SCI) is a devastating condition that results in severe disability and significant comorbidities. The complex pathophysiology of SCI repair and difficulties understanding neural regeneration are treatment challenges. Objectives: The aim of this study is to systematically review the diverse applications of various fish species as models for SCI research. Evidence Acquisition: PRISMA guidelines were used to review observational and interventional studies that utilized fish species as SCI models, published from inception to July 2023. Two independent reviewers screened and performed the data extraction. One independent reviewer assessed the risk of bias for the included studies. Results: Five thousand six hundred and thirty-three records were reviewed, and 144 met the inclusion criteria and were categorized by fish species. The majority of studies employed complete transection injuries, with the remainder being crush injuries, laser injuries, electro-ablations, and demyelination with substances. Zebrafish (Danio rerio) were most commonly utilized 102/144 (71%), primarily with larval models. Other models included Lamprey (Petromyzon marinus and Lethenteron reissneri); Goldfish (Carassius auratus); European eel (Anguilla Anguilla); Knifefish (Apteronotus leptorhynchus and Apteronotus albifrons); Sailfin Molly (Poecilia latipinna); and African turquoise killifish (Nothobranchius furzeri). Conclusions: This systematic review highlights that fish models, particularly zebrafish, goldfish, and European eels, are important models for further defining SCI pathophysiology and regenerative processes. These models provide a less complex model to gain insights into apoptosis and glial networks.

Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury

Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord’s intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SpD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.

Effect of Electrical Stimulation of the Vagus Nerve on Inflammation in Rats With Spinal Cord Injury

ObjectiveThe purpose of this study was to assess the effect of electroacupuncture stimulation (EAS) of the vagus nerve on the inflammatory response in rat models of spinal cord injury (SCI). MethodsThe T10 SCI model in adult male Sprague Dawley rats was established using the modified Allen's method. The EAS group was treated with the therapy on the vagus nerve of rat ear nails, while the SCI group did not receive any EAS treatment. The degree of inflammatory infiltration was reflected by hematoxylin-eosin staining. The inflammatory cytokines in spinal cord tissues, cerebrospinal fluid inflammation, and peripheral blood were detected by enzyme-linked immunosorbent assay. Changes in astrocytes and microglia were assessed using an immunofluorescence assay. ResultsElectroacupuncture stimulation treatment inhibited inflammatory infiltration, as well as the concentrations of interleukin-6, interleukin-1β, tumor necrosis factor-α, astrocytes, and microglia at 1, 6, and 24 hours after 1 EAS treatment. Multiple EAS treatments had an obvious effect on SCI inflammation. ConclusionA single EAS treatment had a limited effect on inflammation, but multiple treatments had a significant inhibitory effect on inflammation.

An innovative electrical neurostimulation approach to mimic reflexive urination control in spinal cord injury models

Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.

Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.

Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.

Nanozyme Hydrogels Promote Nerve Regeneration in Spinal Cord Injury by Reducing Oxidative Stress.

Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Synaptotagmin 4 Supports Spontaneous Axon Sprouting after Spinal Cord Injury.

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function.

Effectiveness of Insolubilized Poly(vinyl alcohol)-Based Electrospun Fiber-Loaded Methylprednisolone by Enzyme-Catalyzed Cross-Linking in a Rat Spinal Cord Injury Model.

Spinal cord injury (SCI) has been implicated in neural loss and, consequently, motor/sensory impairment. Here, we propose an improved formation for fibrous mat fabrication from the derivatives of poly(vinyl alcohol) (PVA) and gelatin (Gela) through horseradish peroxidase-mediated cross-linking, providing a sustained release of methylprednisolone (MP) for SCI repair. After 28 days, the animals were evaluated in terms of remyelination and apoptosis and underwent behavioral tests. The mechanical properties, hydrophobicity, and degradation rate of PVAPh/GelaPh fibrous mats were significantly improved as compared with those of PVAPh samples. This could provide the desired structure for a sustained MP release. The seeded cells could adhere and proliferate to the composite fibers, which indicates the cytocompatibility of the resultant PVAPh/GelaPh fibrous mat. The results showed significant reductions in the number of apoptotic neurons and a substantial improvement in remyelination in the SCI+ PVAPh/GelaPh + MP group. The behavioral tests confirmed improvement in locomotor hindlimb function following treatment. The MP-loaded PVAPh/GelaPh mat developed through the long-term release of MP and the biocompatible fabricated mat could inhibit axonal demyelination, attenuate apoptosis, and improve the functional outcome, which verified the potential of PVAPh/GelaPh + MP nanocomposites as a bioactive scaffold for SCI regeneration.

Magnetic resonance imaging tracing of superparamagnetic iron oxide nanoparticle-labeled mesenchymal stromal cells for repairing spinal cord injury.

Mesenchymal stromal cell transplantation Is an effective and promising approach for treating various systemic and diffuse diseases. However, the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear, including cell viability, distribution, migration, and fate. Conventional cell tracing methods cannot be used in the clinic. The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging. In 2016, the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle, Ruicun, for use as a contrast agent in clinical trials.In the present study, an acute hemi-transection spinal cord injury model was established in beagle dogs. The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells. The results indicated that Ruicun-labeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury. T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord. The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks. These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.

EPIDEMIOLOGY OF SPINAL CORD INJURY AND ASSOCIATED MORTALITY, PAST AND PRESENT. IS THERE A DIFFERENCE?

The demographics of spinal cord injury population has been dynamic over time especially with aging. This study investigated the patterns of SCI admissions by age in the United States over the past decade. Data was evaluated (2010-21), from the National Spinal Cord Injury Model Systems records. Patients were compared based on age (<70 and ≥70 years). Analysis of mortality, neurologic level of injury, neurologic improvement, and mortality by ASIA grade and neurologic level of injury. Patients greater than 70 were defined as elderly. 8,137 patients were reviewed with mean age 42.6 years (range 15-88). The mean admission rate per year was 678 (range 378 -758). For the elderly vs the younger cohort, incidence of fall decreased by 5% vs 3.3%, vehicle accidents increased by 3% vs 14%, high tetraplegia increased by 14.7% vs 22.5%, low tetraplegia decreased by 12% vs 5.7%. In the elderly, ASIA grades A, B and C decreased significantly while ASIA Grade D increased by 23.8%. In the younger cohort ASIA A and B injuries increased while C and D increased, all <5%. Overall, 32.1% of those with ASIA A and 68% with ASIA B injuries improved within one to two years after injury. In-hospital and 1-year mortalities decreased by 14.5% and 35.4% respectively in the elderly. The incidence of SCI increased. High cervical and incomplete injuries increased, while complete spinal cord injuries declined. In-hospital and 1-year mortality decreased. There was recovery in select cases of complete spinal cord injuries within 1 year.

Systematic Review of Peptide CAQK: Properties, Applications, and Outcomes.

Many central nervous system (CNS) disorders lack approved treatment options. Previous research demonstrated that peptide CAQK can bind to chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix of the CNS. In vivo studies have investigated CAQK conjugated to nanoparticles containing therapeutic agents with varying methodologies/outcomes. This paper presents the first systematic review assessing its properties, applications, and outcomes secondary to its use. Following PRISMA guidelines, a comprehensive search was performed across multiple databases. Studies utilizing CAQK as a therapeutic agent/homing molecule in animal/human models were selected. Sixteen studies met the inclusion criteria. Mice and rats were the predominant animal models. All studies except one used CAQK to deliver a therapeutic agent. The reviewed studies mostly included models of brain and spinal cord injuries. Most studies had intravenous administration of CAQK. All studies demonstrated various benefits and that CAQK conjugation facilitated localization to target tissues. No studies directly evaluated the effects of CAQK alone. The data are limited by the heterogeneity in study methodologies and the lack of direct comparison between CAQK and conjugated agents. Overall, these findings present CAQK utilization to deliver a therapeutic agent as a promising targeting strategy in the management of disorders where CSPGs are upregulated.

Substance use during the COVID-19 pandemic among persons with traumatic spinal cord injury: A cross-sectional perspective

Study design: Analysis of data from two cohorts of Spinal Cord Injury Model Systems Database (SCIMS) participants, pre-pandemic (2017–2019, n = 6368) and during pandemic (2020, n = 1889). Objectives: To examine differences in substance use during the pandemic compared to the years prior to the pandemic. Setting: 19 SCIMS Centers. Methods: Participant characteristics, wellness (depression, life satisfaction, resilience), participation, and substance use between the two cohorts were compared. Multiple logistic regression examined the association of the pandemic with substance use after accounting for other factors. Results: Characteristics of the two cohorts were similar. Cannabis and sedative uses were not greatly different (28.8% vs 25.1%, and 8.3% vs 6.6%) but did reach statistical significance. Non-prescribed opioid use was double for the pandemic group (6.6% vs 3.3%). Alcohol use patterns were similar across the two cohorts. Measures of wellness were similar, while the pandemic group reported lower participation. The odds of use of cannabis, sedatives, and opioids were 1.3, 1.3, and 2.2 times greater, respectively, for the pandemic cohort after accounting for demographics, wellness, and participation. Greater use of non-prescribed opioids was reported during the pandemic in the South compared to prior to the pandemic (13.8% vs 6.1%). Conclusions: The pandemic may have been associated with increased use of non-prescribed substances in the traumatic spinal cord injury population. Efforts to pursue longitudinal investigations would be warranted for definitive analysis of trends. The provision of demonstrably effective substance use treatment resources delivered via accessible methods will likely be needed in this population, particularly opioid treatment.

Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation. The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus. Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

Multifunctional conductive stem cell delivery hydrogel combined with low-frequency pulsed electromagnetic fields for spinal cord injury repair

Spinal cord injury (SCI) is a severe traumatic disease for which no satisfying treatment is available. The severe inflammatory reactions and poor endogenous regenerative capacity cause difficulty in functional recovery. Neural stem cells (NSCs) transplantation is currently a promising treatment for repairing SCI. However, there is a lack of effective ways to improve the survival rates of NSCs and promote the neuron differentiation rates of NSCs. Conductive hydrogel can mimic environment which is suitable for neurodevelopment. Low-frequency pulsed electromagnetic fields (LPEMFs) have the advantages of safety, non invasiveness, and tissue repair, making it a potential method of repairing SCI. In this study, an injectable, self-healing magnetic, and conductive hydrogel was synthesized to carry out NSCs with LPEMFs for repairing SCI. In vitro experiments, under the treatment of LPEMFs and conductive hydrogel, the microglia tend to polarize into M2 phenotype, rather than M1 phenotype. Meanwhile, NSCs tend to differentiate into neuronal direction. In SCI model, conductive hydrogel loaded with NSCs combined with LPEMFs can promote functional recovery, through reducing inflammation and promoting neuron differentiation of NSCs. This study provides a novel NSCs transplantation strategy combined with physical interventions for SCI treatment, which brings a new desire to repair SCI.

Wheelchair Repairs: Delays, Causes, and Associated Outcomes

ObjectiveTo examine the length of time to complete wheelchair repairs and the relationship between negative outcomes and the factors that prevented or determined who performed repairs. DesignSurvey, cross-sectional. SettingNine spinal cord injury (SCI) Model Systems Centers. ParticipantsWheelchair users with SCI reporting at least 1 repair (N=301) InterventionsNot applicable Main Outcome MeasuresPrevalence of adverse consequences associated with wheelchair repairs, repairs completed of those needed, and time elapsed before wheelchair repair. Results76% of participants reported all necessary repairs were completed, while 7% indicated that some repairs were addressed, and 14% reported none of the repairs being completed. The most common reason for incomplete repairs (30%) was the vendor's failure to complete the repair after being contacted. Among the repairs that were successfully completed, 56% were performed by vendors. The median time elapsed before repair was 14 days, with no significant difference observed in the time taken for repairs across different components. The most common consequences were being forced to use a backup wheelchair or being confined at home. A greater percentage of participants experienced each type of consequence, except injury, for repairs completed by vendors. ConclusionsThe high percentage of uncompleted wheelchair repairs poses a significant risk to users, and this risk is compounded by prolonged time taken by vendors to address breakdowns. Unsatisfactory vendor service was common, with a significantly larger proportion of participants experiencing consequences for repairs that required a vendor. This seems to indicate structural inadequacies within the repair process and the need for interventions to address these issues.

Natural and bio-engineered stem cell-derived extracellular vesicles for spinal cord injury repair: A meta-analysis with trial sequential analysis

BackgroundStem-cell derived extracellular vesicles (EVs) have shown promise in preclinical spinal cord injury (SCI) models but lack a comprehensive literature review for clinical translation guidance. MethodsThis meta-analysis with trial sequential analysis systematically search PubMed, Web of Science, Embase, and Cochrane Library databases. Prespecified inclusion criteria were studies reporting on measurable outcomes relevant to SCI repair. Risk of bias and quality of reporting were assessed. Random-effects meta-analyses and subgroup analyses comparing natural and bio-engineered EVs were performed. The study was registered with PROSPERO (CRD42024512122). FindingsThe search identified 3935 records, of which 39 studies were included, totaling 1801 animals. Administration of EVs significantly improved locomotor function as measured by Basso-Beattie-Bresnahan or Basso-Mouse-Scale scores at 1 week (natural EVs: SMD 1.50, 95 % CI 1.06–1.95; bio-engineered EVs: SMD 1.93, 95 % CI 1.34–2.52) and 3 weeks (natural EVs: SMD 2.57, 95 % CI 1.96–3.17; bio-engineered EVs: SMD 3.16, 95 % CI 2.29–4.02) post-injury. Subgroup analyses indicated surface modification approaches were most effective among bio-engineered EV strategies. EVs also promoted nerve growth (SMD 2.95, 95 % CI 2.12–3.78), enhanced neuron conductivity (MD 0.75, 95 %CI 0.59–0.90), alleviated inflammation (SMD −3.12, 95 % CI −4.15--2.10), and reduced lesion size (SMD −2.90, 95 % CI −3.87--1.93). ConclusionsBoth natural and bio-engineered EVs improve functional and pathological outcomes in animal models of SCI. The enhanced benefits observed with bio-engineered EVs, particularly those utilizing surface modification approaches, highlight the importance of continued exploration into bio-engineering techniques to optimize EVs’ therapeutic efficacy for SCI repair.Protocol RegistrationCRD42024512122.

Development and validation of a novel nomogram for predicting mechanical ventilation after cervical spinal cord injury

ObjectiveThis study aimed to investigate the risk factors relating to the need for mechanical ventilation (MV)in isolated cervical spinal cord injury (cSCI) patients and to construct a nomogram prediction model. DesignRetrospective analysis study. ParticipantsA total of 5784 patients (N=5784) who had a cSCI were admitted to the National Spinal Cord Injury Model System database (NSCID) between 2006 and 2021. SettingNSCID observation data was initially collected during rehabilitation hospitalization. InterventionsNot applicable. Main Outcome Measure(s)A univariate and multivariate logistic regression analysis was used to identify the independent factors affecting the use of MV in cSCI patients, these independent influencing factors were used to develop a nomogram prediction model. The area under the receivers operating characteristic curve (AUROC), calibration curve and decision curve analysis (DCA) were employed to evaluate the efficiency and the clinical application value of the model respectively. ResultsIn a series of 5784 included patients, 926 cases (16.0%) were admitted to spinal cord model system inpatient rehabilitation with the need of MV. Logistic regression analysis demonstrated that associated injury, American Spinal Cord Injury Association (ASIA) impairment scale (AIS), the sum of unilateral optimal motor scores for each muscle segment of upper extremities (sUEM) and neurological level of injury (NLI) were independent predictors of the use of MV (p<0.05). The prediction nomogram of MV usage in cSCI patients was established based on the above independent predictors. The AUROC of the training set, internal verification set and external verification set were 0.871 (0.857-0.886), 0.867 (0.843-0.891) and 0.850 (0.824-0.875) respectively. The calibration curve and DCA results showed that the model had a good calibration and clinical practicability. ConclusionThe nomograph prediction model based on sUEM, NLI, associated injury and AIS can accurately and effectively predict the risk of MV in cSCI patients, to help clinicians screen high-risk patients and formulate targeted intervention measures.