Carboxymethyl cellulose/quaternized chitosan hydrogel loaded with polydopamine nanoparticles promotes spinal cord injury recovery by anti-ferroptosis and M1/M2 polarization modulation.

Spinal cord injury (SCI) represents a catastrophic neurological condition resulting in long-term loss of motor, autonomic, and sensory functions. Recently, ferroptosis, an iron-regulated form of cell death distinct from apoptosis, has emerged as a potential therapeutic target for SCI. In this study, we developed an injectable hydrogel composed of carboxymethyl cellulose (CMC), and quaternized chitosan (QCS), loaded with modified polydopamine nanoparticles (PDA NPs), referred to as CQP hydrogel. This hydrogel effectively scavenged reactive oxygen species (ROS), prevented the accumulation of Fe2+ and lipid peroxidation associated with ferroptosis, and restored mitochondrial functions in primary neuronal cells. When administered to animal models (rats) with SCI, the CQP hydrogels improved motor function by regulating iron homeostasis, inhibiting ferroptosis, and mitigating oxidative stress injury. Both in vitro and in vivo studies corroborated the capacity of CQP hydrogels to promote the shift from M1 to M2 polarization of microglia/macrophages. These findings suggest that CQP hydrogels, functioning as a localized iron-chelating system, have potential as biomaterials to enhance recovery from SCI by targeting ferroptosis and modulating anti-inflammatory macrophages activity.

Effect of iTBS dual-target stimulation on lower limb function in patients with incomplete spinal cord injury:a randomized, single-blind,sham-controlled study.

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

Neuroprotective macromolecular methylprednisolone prodrug nanomedicine prevents glucocorticoid-induced muscle atrophy and osteoporosis in a rat model of spinal cord injury.

To address the adverse side effects associated with systemic high-dose methylprednisolone (MP) therapy for acute spinal cord injury (SCI), we have developed a N-2-hydroxypropyl methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP). Intravenous Nano-MP selectively targeted to the inflamed SCI lesion and significantly improved neuroprotection and functional recovery after acute SCI. In the present study, we comprehensively assessed the potential adverse side effects associated with the treatment in the SCI rat models, including reduced body weight and food intake, impaired glucose metabolism, and reduced musculoskeletal mass and integrity. In contrast to free MP treatment, intravenous Nano-MP after acute SCI not only offered superior neuroprotection and functional recovery but also significantly mitigated or even eliminated the aforementioned adverse side effects. The superior safety features of Nano-MP observed in this study further confirmed the clinical translational potential of Nano-MP as a highly promising drug candidate for better clinical management of patients with acute SCI.

Exosomal miR-17-92 Cluster from BMSCs Alleviates Apoptosis and Inflammation in Spinal Cord Injury.

Spinal cord injury (SCI) involves neuronal apoptosis and axonal disruption, leading to severe motor dysfunction. Studies indicate that exosomes transport microRNAs (miRNAs) and play a crucial role in intercellular communication. This study aimed to explore whether the bone marrow mesenchymal stem cell (BMSCs)-exosomal miR-17-92 cluster can protect against SCI and to explain the underlying mechanisms. In vivo and in vitro SCI models were established and treated with control exosomes (con-exo) or exosomes derived from BMSCs transfected with miR-17-92 cluster plasmid (miR-17-92-exo). Rat BMSCs were isolated and positive markers were identified by flow cytometry. BMSC-derived exosomes were extracted and verified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The expression of the miR-17-92 cluster was validated by quantitative reverse transcription PCR (qRT-PCR). Spinal cord function, histopathological changes, apoptotic cells, and inflammatory cytokines release in spinal cord tissues were assessed using the Basso-Beattie-Bresnahan (BBB) score, hematoxylin and eosin (HE) staining, terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR. In PC12 cells, cell proliferation, apoptosis, apoptosis-related proteins cleaved-Caspase3 expression, and inflammatory factors secretion were analyzed using a cell counting kit-8 (CCK8) assay, flow cytometry, western blotting, and ELISA. Our data revealed that the exosomes were successfully isolated from rat BMSCs. The BMSC-exosomal miR-17-92 cluster improved neural functional recovery after SCI, as evidenced by an increased BBB score, improved pathological damage, reduced neuronal apoptosis, and decreased inflammatory factors release. Additionally, miR-17-92-exo treatment significantly inhibited lipopolysaccharide (LPS)-induced reduction in cell viability, increase in cell apoptosis, and upregulation of inflammatory factors in PC12 cells. The exosomal miR-17-92 cluster derived from BMSCs improved functional recovery and exhibited neuroprotective effects in SCI by alleviating apoptosis and inflammation.

The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

INTRODUCTION: There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. METHODS: This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. RESULTS: Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. CONCLUSION: This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. PATIENT AND PUBLIC INVOLVEMENT STATEMENT: This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

Effects of exoskeleton-assisted walking on bowel function in motor-complete spinal cord injury patients: involvement of the brain-gut axis, a pilot study.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.

Mechanism Analysis of Selenium-Containing Compounds in Alleviating Spinal Cord Injury Based on Network Pharmacology and Molecular Docking Technology.

Spinal cord injury (SCI) is a severe traumatic condition in spinal surgery characterized by nerve damage in and below the injured area. Despite advancements in understanding the pathophysiology of SCI, effective clinical treatments remain elusive. Selenium compounds have become a research hotspot due to their diverse medicinal activities. Previously, our group synthesized a selenium-containing Compound 34# with significant anti-inflammatory activity. This study aimed to explore the anti-SCI effects of selenium-containing compounds using network pharmacology, molecular docking (MD), and ADMET methods. To identify SCI-related targets and those associated with 34#, GeneCards, NCBI, and SEA databases were employed. Eight overlapping targets were considered candidate targets, and molecular docking was performed using the PDB database and AutoDock software. The STRING database was used to obtain protein-protein interactions (PPI). Molecular dynamics simulation, MM/GBSA binding free energy score, and ADMET prediction were used to evaluate the potential targets and drug properties of 34#. Finally, experiments on NSC34 cells and mice were to verify the effects of 34# on SCI. Our results revealed eight candidate targets for 34# in the treatment of SCI. PPI and MD identified ADRB2 and HTR1F as the highest connectivity with 34#. ADMET analysis confirmed the low toxicity and safety of 34#. In vitro and in vivo models validated the anti-SCI effects. Our study elucidated candidate targets for alleviating SCI with 34#, explored PPI and target-related signaling pathways, and validated its anti-SCI effects. These findings enhance our understanding of 34#'s mechanism in treating SCI, positioning it as a potential candidate for SCI prevention.

Electrical Stimulation and Motor Function Rehabilitation in Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) often leads to devastating motor impairments, significantly affecting the quality of life of affected individuals. Over the last decades, spinal cord electrical stimulation seems to have encouraging effects on the motor recovery of impacted patients. This review aimed to identify clinical trials focused on motor function recovery through the application of epidural electrical stimulation, transcutaneous electrical stimulation, and functional electrical stimulation. Several clinical trials met these criteria, focusing on the impact of the aforementioned interventions on walking, standing, swimming, trunk stability, and upper extremity functionality, particularly grasp. After a thorough PubMed online database research, 37 clinical trials were included in this review, with a total of 192 patients. Many of them appeared to have an improvement in function, either clinically assessed or recorded through electromyography. This review outlines the various ways electrical stimulation techniques can aid in the motor recovery of SCI patients. It stresses the ongoing need for medical research to refine these techniques and ultimately enhance rehabilitation results in clinical settings.

Activity limitations, participation restrictions, and environmental barriers among persons with traumatic spinal cord injury in Kenya.

PURPOSE: Spinal cord injury (SCI) is a life-changing condition, almost always leading to disability. The aim was to determine the period-prevalence of activity limitations, participation restrictions, and environmental barriers in community-dwelling persons with traumatic spinal cord injury (TSCI) in Kenya. METHODS: A cross-sectional survey of 90 community-dwelling adult persons living with TSCI for more than 1 year, recruited from the database of the only specialised rehabilitation, in-patient, facility in Kenya. Modules of the International Spinal Cord Injury community survey (InSCI) used were demographic and injury characteristics; activity and participation; and environmental factors. RESULTS: Most prevalent activity limitations and participation restrictions in the total sample were using public transportation (90%), standing unsupported (83%), getting to destination (76%), and toileting (76%). The top environmental barriers were inadequate finances (96%), inaccessibility of public places (92%), and problems with long distance transportation (90%). Participants with tetraplegia were more affected with activity limitations and participation restrictions than those with paraplegia. CONCLUSION: Functioning problems and environmental barriers are prevalent among adults living with TSCI in Kenya. Although this is the best-case scenario with respect to healthcare services, where individuals received inpatient rehabilitation previously, a need exists to examine the principles and models of rehabilitation and explore the value proposition of primary care/community level rehabilitation to further optimise independence and functioning.

The functioning problems of persons with spinal cord injury (SCI) in Kenya appear to be diverse in nature, which calls for the evaluation of current rehabilitation services and models with the aim of bolstering independence and participation by including evidence-based interventions to standard treatment packages.A high degree of experiencing environmental challenges was found, calling for a whole-of-government approach to enhance inclusivity of persons with SCIs in society.It appears that additional resources or equity measures are allocated to persons with tetraplegia due to their accentuated experience of disability and negative environmental factors.

Urodynamic analysis of the effect of electroacupuncture at different acupoints on the bladder after spinal cord injury.

OBJECTIVE: Guanyuan (CV4), Zhongji (CV3) and Sanyinjiao (SP6) are the most frequently used acupoints for treating neurogenic bladder after spinal cord injury (SCI). However, there has been no investigation to clarify the differences in effects of these acupoints in different types of neurogenic bladder. METHODS: The study was structured with a randomized, two-phase cross over design with a washout period. A routine urodynamic examination was performed first, then, in the order of grouping, electroacupuncture was performed on CV4, CV3, and SP6, respectively，and urodynamic examination was performed to observe the changes of urodynamic indexes in real time. RESULTS: When undergoing electroacupuncture at CV4, CV3, and SP6 in patients with neurogenic detrusor overactivity (DO), the bladder volume at the first occurrence of DO and maximum cystometric capacity increased (p < 0.05), but maximum detrusor pressure (Pdetmax) at DO decreased (p < 0.05), and the changes using CV4 and CV3 was more significantly than using SP6 (p < 0.05). And in patients with in neurogenic detrusor underactivity, there were no significant changes in maximum urinary flow rate and Pdetmax during urination (p > 0.05). CONCLUSION: The immediate relief effect of electroacupuncture at CV4, CV3 on DO was greater than at SP6.

Cross-Cultural Adaptation and Psychometric Validation of the Quality of Life Index Among Hausa-Speaking People with Spinal Cord Injury in Northwest Nigeria.

Background: Quality of life (QoL) is an important outcome that is used to measure the success of healthcare interventions. Valid and reliable instruments are required to assess QoL. Hence, we conducted this study to adapt and validate the QoL Index (QLI) among Hausa-speaking people with spinal cord injury (SCI) in northwest Nigeria. Method: Using the International Society for Pharmacoeconomic and Outcome Research principles of good practice and the consensus-based standards for the selection of health measurement instruments guidelines, the QLI-SCI version was translated into Hausa language and tested for content validity, internal consistency, and test-retest reliability among people with SCI in northwest Nigeria. Result: The Hausa QLI (HQLI) demonstrated good content validity (CVI = 92.18%), internal consistency (Cronbach's alpha = 0.855), and test-retest reliability (ICC =0.949 [95% CI, 0.916-0.969]). Conclusion: The HQLI can be deployed to assess QoL among Hausa-speaking people with SCI, thus promoting robust measurement of QoL in an SCI population.

Formoterol alters chemokine expression and ameliorates pain behaviors after moderate spinal cord injury in female mice.

Secondary spinal cord injury (SCI) is characterized by increased cytokines and chemokines at the site of injury that have been associated with the development of neuropathic pain. Nearly 80% of SCI patients report suffering from chronic pain, which is poorly managed with available analgesics. While treatment with the FDA-approved ß2-adrenergic receptor agonist, formoterol, improves various aspects of recovery post-SCI in vivo, its effects on cytokines, chemokines and neuropathic pain remain unknown. Female mice were subjected to moderate (60 kdyn) or severe (80 kdyn) SCI followed by daily treatment with vehicle or formoterol (0.3 mg/kg, i.p.) beginning 8h after injury. The expression of pro-inflammatory cytokines/chemokines, such as IP-10, MIP-1a, MCP-1, BCA-1 and NF-κB, was increased in the injury site of vehicle-treated mice 24h post-SCI, which was ameliorated with formoterol treatment, regardless of injury severity. Thermal hyperalgesia and mechanical allodynia, as measured by Hargreaves infrared apparatus and von Frey filaments, respectively, were assessed prior to SCI and then weekly beginning 21 days post injury (DPI). While all injured mice exhibited decreased withdrawal latency following thermal stimulation compared to baseline, formoterol treatment reduced this response ~15% by 35 DPI. Vehicle-treated mice displayed significant mechanical allodynia, as evidenced by a 55% decrease in withdrawal threshold from baseline. In contrast, mice treated with formoterol maintained a consistent withdrawal time at all times tested. These data indicate that formoterol reduces inflammation post-SCI, likely contributing to mitigation of neuropathic pain, and further supporting the therapeutic potential of this treatment strategy. Significance Statement Chronic pain is a detrimental consequence of spinal cord injury (SCI). We show that treatment with the FDA-approved drug formoterol after SCI decreases injury site pro-inflammatory chemo/cytokines and alters markers of glial cell activation and infiltration. Additionally, formoterol treatment improves locomotor function and body composition, and decreases lesion volume. Finally, formoterol treatment decreased mechanical allodynia and thermal hyperalgesia post-SCI. These data are suggestive of the mechanism of formoterol-induced recovery, and further indicate its potential as a therapeutic strategy for SCI.

Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis.

OBJECTIVE: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. METHODS: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. RESULTS: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway's critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. CONCLUSION: In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Non-invasive Transcutaneous Spinal Cord Stimulation Programming Recommendations for the Treatment of Upper Extremity Impairment in Tetraplegia.

OBJECTIVES: This study analyzes the stimulation parameters implemented during two successful trials that used non-invasive transcutaneous spinal cord stimulation (tSCS) to effectively improve upper extremity function after chronic spinal cord injury (SCI). It proposes a framework to guide stimulation programming decisions for the successful translation of these techniques into the clinic. MATERIALS AND METHODS: Programming data from 60 participants who completed the Up-LIFT trial and from 17 participants who subsequently completed the LIFT Home trial were analyzed. All observations of stimulation amplitudes, frequencies, waveforms, and electrode configurations were examined. The incidence of adverse events and relatedness to stimulation parameters is reported. A comparison of parameter usage across the American Spinal Injury Association Impairment Scale (AIS) subgroups was conducted to evaluate stimulation strategies across participants with varying degrees of sensorimotor preservation. RESULTS: Active (cathodal) electrodes were typically placed between the C3/C4 and C6/C7 spinous processes. Most sessions featured return (anodal) electrodes positioned bilaterally over the anterior superior iliac spine, although clavicular placement was frequently used by 12 participants. Stimulation was delivered with a 10-kHz carrier frequency and typically a 30-Hz burst frequency. Biphasic waveforms were used in 83% of sessions. Average stimulation amplitudes were higher for biphasic waveforms. The AIS B subgroup required significantly higher amplitudes than did the AIS C and D subgroups. Device-related adverse events were infrequent, and not correlated with specific waveforms or amplitudes. Within the home setting, participants maintained their current amplitudes within 1% of the preset values. The suggested stimulation programming framework dictates the following hierarchical order of parameter adjustments: current amplitude, waveform type, active/return electrode positioning, and burst frequency, guided by clinical observations as required. CONCLUSIONS: This analysis summarizes effective stimulation parameters from the trials and provides a decision-making framework for clinical implementation of tSCS for upper extremity functional restoration after SCI. The parameters are aligned with existing literature and proved safe and well tolerated by participants.

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop.

Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.

Research progress and prospects of benefit-risk assessment methods for umbilical cord mesenchymal stem cell transplantation in the clinical treatment of spinal cord injury.

Over the past decade, we have witnessed the development of cell transplantation as a new strategy for repairing spinal cord injury (SCI). However, due to the complexity of the central nervous system (CNS), achieving successful clinical translation remains a significant challenge. Human umbilical cord mesenchymal stem cells (hUMSCs) possess distinct advantages, such as easy collection, lack of ethical concerns, high self-renewal ability, multilineage differentiation potential, and immunomodulatory properties. hUMSCs are promising for regenerating the injured spinal cord to a significant extent. At the same time, for advancing SCI treatment, the appropriate benefit and risk evaluation methods play a pivotal role in determining the clinical applicability of treatment plans. Hence, this study discusses the advantages and risks of hUMSCs in SCI treatment across four dimensions-comprehensive evaluation of motor and sensory function, imaging, electrophysiology, and autonomic nervous system (ANS) function-aiming to improve the rationality of relevant clinical research and the feasibility of clinical translation.

Significance of physical factors on activities of daily living in patients with tetraplegia after spinal cord injury: a retrospective study.

BACKGROUND: Tetraplegia is a debilitating sequela of spinal cord injury (SCI). However, comprehensive approaches for determining the influence of various factors on activities of daily living (ADL) in patients with tetraplegia are limited. Therefore, this study aimed to determine the influence of physical factors on ADL in patients with tetraplegia after adjusting for demographic, SCI-related, and cognitive factors. METHODS: This retrospective cross-sectional study enrolled 201 patients with tetraplegia who underwent inpatient rehabilitation at the National Rehabilitation Center in South Korea between 2019 and 2021. Patients' mean age was 50.5 years (standard deviation, 16.3), and 170 (84.6%) were men. The Korean Spinal Cord Independence Measure III (K-SCIM III) was used as the main outcome measure to assess patients' ADL ability. Hierarchical multiple regression modeling was conducted with K-SCIM as the dependent variable to examine the level of functioning and relative influencing factors. RESULTS: Upper-extremity motor score (UEMS), upper-extremity spasticity and sitting balance scores were significant predictors of self-care; lower-extremity motor score (LEMS), musculoskeletal pain of shoulder, and sitting balance were significant predictors of respiratory and sphincter management; UEMS, LEMS, and sitting balance score were significant predictors of mobility; and UEMS, LEMS, musculoskeletal pain of shoulder, and sitting balance scores were significant predictors of the K-SCIM III total score after adjustment for demographic, SCI-related, and cognitive factors. CONCLUSIONS: Physical factors had the greatest impact on all subscores and the K-SCIM III total score. Upper- and lower-extremity muscle strength and sitting balance significantly affected functional ability across all subscores.

Perspectives of people with spinal cord injury on a pain education resource.

Introduction: Spinal cord injury (SCI) often leads to neuropathic pain that negatively affects quality of life. Several qualitative research studies in individuals with SCI who experience neuropathic pain indicate the lack of adequate information about pain. We previously developed an educational resource, the SeePain, based on scientific literature and a series of qualitative interviews of people with SCI, their significant others/family members, and SCI healthcare providers. Methods: However, to quantitatively evaluate the utility of this educational resource in a larger sample, we examined the agreement and usefulness ratings of statements regarding clarity/comprehensibility, content, and format of the SeePain, derived from the thematic analysis of our previous qualitative interviews. Participants completed a survey that provided a digital version of the SeePain and then rated their agreement/usefulness with the statements using numerical rating scales. Results: There were overall high perceived agreement and usefulness ratings regarding the SeePain's clarity, content, and format. A factor analysis reduced the agreement and usefulness ratings into 4 components (content, clarity, format, and delivery medium). Group comparisons showed that individuals with higher education were more likely to endorse electronic and website formats, and the usefulness of a shorter version of the SeePain; females and younger individuals showed greater endorsement for clarity. Finally, higher pain intensity ratings were associated with greater agreement and usefulness of the content of the SeePain. Discussion: Overall, these results support the utility of the SeePain as a source of information regarding pain that may facilitate communication about pain and its management following SCI.

A pilot study for testing feasibility and preliminary influence of early intervention using text messaging for pressure ulcer prevention in individuals with spinal cord injury.

BACKGROUND: This pilot study assessed text messaging as an early intervention for preventing pressure ulcers (PrUs) in individuals with spinal cord injury (SCI) post-hospital discharge. METHOD: Thirty-nine wheelchair-users discharged after acquiring a SCI, underwent randomisation into an intervention group (n = 20) with text messages and a control group (n = 19). All participants received standard post-discharge care and completed a skincare questionnaire before and 6-month after discharge. Primary outcomes included feasibility and acceptability of early intervention using text messaging, alongside performance, concordance, and attitudes toward skincare. Secondary outcomes measured perception and the incidence of PrUs. RESULTS: Baseline demographics were comparable between the intervention and control groups. Eight of 20 participants completed 6-month follow-up questionnaires in the intervention group, six participants completed the 6-month questionnaires in the control group,. Participants expressed high satisfaction with text messages, understanding of content, and increased confidence in preventing PrUs. At 6-month post-discharge, the intervention group showed improved prevention practices, heightened awareness of PrU risks, and increased perceived importance of prevention, which were not observed in the control group. However, there were no significant differences in PrU incidence, possibly due to the small sample size and short follow-up. CONCLUSION: The study demonstrates that using text messaging as an early intervention for PrU prevention in individuals with SCI is feasible and well-received. Preliminary results suggest a positive impact on participants' attitudes and practices, indicating the potential of text messaging to reduce PrU incidence. However, further research with larger samples and extended follow-up is crucial to validate these promising initial findings.