Phillygenin inhibits neuroinflammation and promotes functional recovery after spinal cord injury via TLR4 inhibition of the NF-κB signaling pathway.

Background: Spinal cord injuries (SCIs) trigger a cascade of detrimental processes, encompassing neuroinflammation and oxidative stress (OS), ultimately leading to neuronal damage. Phillygenin (PHI), isolated from forsythia, is used in a number of biomedical applications, and is known to exhibit anti-neuroinflammation activity. In this study, we investigated the role and mechanistic ability of PHI in the activation of microglia-mediated neuroinflammation and subsequent neuronal apoptosis following SCI. Methods: A rat model of SCI was used to investigate the impact of PHI on inflammation, axonal regeneration, neuronal apoptosis, and the restoration of motor function. In vitro, neuroinflammation models were induced by stimulating microglia with lipopolysaccharide (LPS); then, we investigated the influence of PHI on pro-inflammatory mediator release in LPS-treated microglia along with the underlying mechanisms. Finally, we established a co-culture system, featuring microglia and VSC 4.1 cells, to investigate the role of PHI in the activation of microglia-mediated neuronal apoptosis. Results: In vivo, PHI significantly inhibited the inflammatory response and neuronal apoptosis while enhancing axonal regeneration and improving motor function recovery. In vitro, PHI inhibited the release of inflammation-related factors from polarized BV2 cells in a dose-dependent manner. The online Swiss Target Prediction database predicted that toll-like receptor 4 (TLR4) was the target protein for PHI. In addition, Molecular Operating Environment software was used to perform molecular docking for PHI with the TLR4 protein; this resulted in a binding energy interaction of -6.7 kcal/mol. PHI inhibited microglia-mediated neuroinflammation, the production of reactive oxygen species (ROS), and activity of the NF-κb signaling pathway. PHI also increased mitochondrial membrane potential (MMP) in VSC 4.1 neuronal cells. In BV2 cells, PHI attenuated the overexpression of TLR4-induced microglial polarization and significantly suppressed the release of inflammatory cytokines. Conclusion: PHI ameliorated SCI-induced neuroinflammation by modulating the TLR4/MYD88/NF-κB signaling pathway. PHI has the potential to be administered as a treatment for SCI and represents a novel candidate drug for addressing neuroinflammation mediated by microglial cells. The translational potential of this article: We demonstrated that PHI is a potential drug candidate for the therapeutic management of SCI with promising developmental and translational applications.

Monitoring muscle activity in pediatric SCI: Insights from sensorized rocking chairs and machine-learning.

Introduction: Activity-based therapy is effective at improving trunk control in children with spinal cord injury. A prototype sensorized rocking chair was developed and confirmed as an activity that activates trunk muscles. This study uses data collected from the chair to predict muscle use during rocking. Methods: The prototype rocking chair included sensors to detect forces, accelerations, as well child and chair movement. Children with spinal cord injury and typically developing children (2-12 years), recruited under an approved IRB protocol, were observed rocking while sensor and electromyography data were collected from arm, leg, and trunk muscles. Features from sensor data were used to predict muscle activation using multiple linear regression, regression learning, and neural network modeling. Correlation analysis examined individual sensor contributions to predictions. Results: Neural network models outperformed regression models. Multiple linear regression predictions significantly correlated (p < 0.05) with targets for four of eleven children with SCI, while decision tree regression predictions correlated for five children. Neural network predictions correlated for all children. Conclusions: Embedded sensors capture useful information about muscle activation, and machine learning techniques can be used to inform therapists. Further work is warranted to refine prediction models and to investigate how well results can be generalized.

A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy.

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

Pharmacological management of secondary chronic spinal cord injury: a systematic review.

INTRODUCTION: Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. SOURCE OF DATA: Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. AREAS OF AGREEMENT: Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. AREAS OF CONTROVERSY: The management of secondary chronic SCI is challenging, with unpredictable outcomes. GROWING POINTS: Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. AREAS TIMELY FOR DEVELOPING RESEARCH: Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.

NEMO-Binding Domain/IKKγ Inhibitory Peptide Alleviates Neuronal Pyroptosis in Spinal Cord Injury by Inhibiting ASMase-Induced Lysosome Membrane Permeabilization.

A short peptide termed NEMO-binding domain (NBD) peptide has an inhibitory effect on nuclear factor kappa-B (NF-κB). Despite its efficacy in inhibiting inflammatory responses, the precise neuroprotective mechanisms of NBD peptide in spinal cord injury (SCI) remain unclear. This study aims to determine whether the pyroptosis-related aspects involved in the neuroprotective effects of NBD peptide post-SCI.Using RNA sequencing, the molecular mechanisms of NBD peptide in SCI are explored. The evaluation of functional recovery is performed using the Basso mouse scale, Nissl staining, footprint analysis, Masson's trichrome staining, and HE staining. Western blotting, enzyme-linked immunosorbent assays, and immunofluorescence assays are used to examine pyroptosis, autophagy, lysosomal membrane permeabilization (LMP), acid sphingomyelinase (ASMase), and the NF-κB/p38-MAPK related signaling pathway.NBD peptide mitigated glial scar formation, reduced motor neuron death, and enhanced functional recovery in SCI mice. Additionally, NBD peptide inhibits pyroptosis, ameliorate LMP-induced autophagy flux disorder in neuron post-SCI. Mechanistically, NBD peptide alleviates LMP and subsequently enhances autophagy by inhibiting ASMase through the NF-κB/p38-MAPK/Elk-1/Egr-1 signaling cascade, thereby mitigating neuronal death. NBD peptide contributes to functional restoration by suppressing ASMase-mediated LMP and autophagy depression, and inhibiting pyroptosis in neuron following SCI, which may have potential clinical application value.

Nuances of gender affirming therapy for transgender women with spinal cord injury.

CASE DESCRIPTION: 56-year-old transgender woman with new spinal cord injury (SCI) on gender affirming hormonal therapy (GAHT) with estrogen and spironolactone. FINDINGS: After her injury, estrogen and spironolactone were discontinued, for blood clots and hypotension, respectively. Alternative options were explored. CLINICAL RELEVANCE: Little is known about GAHT in SCI for transgender women. Shared decision making should be used to navigate risks, benefits, and alternative options.

Impact of secondary health conditions on the quality of life and wellbeing of Canadians living with spinal cord injury: A comparison of preference-weighted index scores derived from generic standardized instruments.

CONTEXT/OBJECTIVES: To compare the assessment of the impact of secondary health conditions (SHCs) on the quality of life and wellbeing of Canadians living with spinal cord injury (SCI) using four preference-based outcome measures. DESIGN: Secondary analysis of data from a cross-sectional, online survey. SETTING: Community. PARTICIPANTS: Community-dwelling adults (n = 364) living with traumatic or non-traumatic spinal cord injury at least one year post-injury (70% at least 10 years post-injury). OUTCOME MEASURES: A modified version of the Spinal Cord Injury Secondary Conditions Scale (SCI-SCS); three health-related instruments (EQ-5D-5L, Health Utilities Index Mark 3 (HUI3), and the Assessment of Quality of Life 8-dimension questionnaire (AQoL-8D)) and a capability wellbeing instrument (ICEpop CAPability measure for Adults (ICECAP-A)). RESULTS: Across unadjusted and controlled analyses (i.e. controlling for associations between index scores and sociodemographic and impairment characteristics), trends were observed that identified lower levels of quality of life/wellbeing with higher problem ratings for each of the SHCs. Despite the trends, there was considerable variation in mean index scores across instruments, with HUI3 scores the lowest of the health-related instruments and ICECAP-A scores the highest overall. Respiratory problems, depression/mood problems, pressure sores, and autonomic dysreflexia were associated with the lowest levels of quality of life and wellbeing. CONCLUSIONS: Higher problem ratings for SHCs are negatively associated with scores derived from preference-based quality of life and wellbeing instruments. Variation in index scores across instruments - including across the health-related instruments alone - highlights the critical importance of assessing the relative merits of preference-based instruments when using (or considering using) these instruments/estimates in comparative effectiveness research and economic evaluation.

The efficacy, safety, and satisfaction of telehealth-delivered hypnotic cognitive therapy for chronic pain in spinal cord injury: A pilot study with historical controls.

CONTEXT/OBJECTIVE: In-person hypnotic cognitive therapy (HYP-CT) is a promising treatment for chronic spinal cord injury-related pain. We describe the effects of HYP-CT delivered via Zoom (Z-HYP-CT) and compare the effects to historical controls who received hypnosis, cognitive therapy, or HYP-CT in-person. DESIGN: Open pilot trial of HYP-CT versus historical controls. SETTING: Telehealth study that recruited people with chronic SCI. PARTICIPANTS: Adults with moderate to severe chronic SCI-related pain. INTERVENTIONS: Four weekly sessions of HYP-CT delivered via Zoom. OUTCOME MEASURES: The primary outcome was average pain intensity on a 0-10 numerical rating scale measured at end of treatment (4 weeks) and 12 weeks. Secondary outcomes included pain interference, depression, sleep, pain catastrophizing, and pain self-efficacy. RESULTS: 23 individuals with SCI-related pain participated in the open trial and were compared to 21 historical controls. Average age was 54 years, 70% were male, and the majority were White. The participants were 11.6-13.1 years post-SCI and average pain intensity was 4.8-5.4/10. After Z-HYP-CT mixed-effects linear regressions showed that pain intensity was significantly less at 4 weeks (-1.28, P < .0001) and 12 weeks (-1.50, P < .0001) relative to baseline. Pain interference, depression, and pain catastrophizing also decreased significantly at both time points. There were no significant differences between the effects of Z-HYP-CT versus historical controls on any outcome variable. CONCLUSION: HYP-CT delivered via telehealth was associated with reduced pain intensity and other benefits that were comparable to the effect achieved by in-person historical controls. The effects of Z-HYP-CT should be evaluated using a randomized controlled design.

Professionals' knowledge, skills and confidence on using the best practices for spinal cord injury physical activity counseling in Canada and the Netherlands.

CONTEXT: To improve physical activity (PA) participation in people with spinal cord injury (SCI), an international panel co-created theory- and evidence-based best practices for SCI PA counseling. This study aimed to identify and compare Canadian and Dutch counselors' knowledge, skills, and confidence in using these best practices. METHODS: An online survey was conducted in Canada and the Netherlands. Respondents were included if they worked or volunteered as exercise/lifestyle counselor, recreation therapist, physiotherapist, occupational therapist, or peer mentor and were planning to provide counseling in the next 12 months. Chi-square tests, t-tests and linear regression analyses were used to compare groups. RESULTS: Canadian (n = 45) and Dutch respondents (n = 41) had different expertise, with the majority of Canadians working as therapeutic recreation therapist and the majority of Dutch respondents working as PA/lifestyle counselor. In both countries, respondents scored relatively high on their knowledge, skills, and confidence in using the best practices on how to have a conversation and what to discuss during a conversation. Dutch respondents scored slightly higher in their confidence for using best practices about building rapport, motivational interviewing, and tailoring the support (p = 0.05). CONCLUSIONS: The generally high counseling skills reported by Canadian and Dutch respondents may be due to the history of SCI-specific PA promotion projects conducted in both countries. These survey findings were used to inform the development of evidence-based training modules on SCI PA counseling. This study may inspire cross-country collaboration and exchange to optimize the organization and delivery of PA counseling services for adults with SCI.

Nocturia and obstructive sleep apnea in spinal cord injured patients - a cohort study.

PURPOSE: To describe the prevalence of nocturia and obstructive sleep apnea (OSA) in a cohort of spinal cord injury (SCI) patients and to describe their association. Additionally, to assess clinical and urodynamic data explaining nocturia and to evaluate the effect of OSA management with continuous positive airway pressure (CPAP). METHOD: Retrospective analysis of data from patients with SCI followed in a tertiary care rehabilitation center with a specialized sleep and neuro-urology units. All adult SCI patients who underwent urodynamic assessment before polysomnography (PSG) between 2015 and 2023 were eligible. Subjective (nocturia) and objective data (urodynamic data, polysomnography, CPAP built-in software) were collated from the Handisom database (database register no. 20200224113128) and the medical records of SCI patients. Statistical testing used Mann-Whitney test for non-parametric variables, Fisher's exact test for contingency analysis and the Spearman correlation test to assess correlations. A p-value < 0.05 was considered significant. Statistical analyses were performed using GraphPad Prism v9. RESULTS: 173 patients (131 males, 42 females) were included. The majority of patients were paraplegic (n = 111 (64,2%)) and had complete lesions (n = 75 (43,4%)). A total of 100 patients had nocturia (57,5%). The prevalence of OSA (Apnea Hypopnea Index (AHI) ≥ 15/h) in the studied population was 61,9%. No correlation was found between nocturia and OSA. A significant difference was observed between patients with and without nocturia in terms of the presence of neurogenic detrusor overactivity (p = 0,049), volume at the first detrusor contraction (p = 0,004) and the bladder functional capacity (p < 0,001). CONCLUSION: Nocturia and OSA are highly prevalent in patients with SCI, but no statistical association was found between these two disorders. A prospective study focusing on nocturnal polyuria will be needed to assess the impact of OSA on lower urinary tract symptoms in SCI patients.

Role of Autologous Platelet-Rich Fibrin in Chronic Non-healing Ulcers With Various Etiologies in a Tertiary Care Rehabilitation Centre: A Case Series.

Introduction Chronic non-healing ulcers are defined as a discontinuity or break in the integrity of skin that is not healing in a reasonable period of time due to an underlying systemic etiology. Despite using conventional initial treatment and many other available dressing options, such wounds are difficult to completely heal, thus affecting the progress of rehabilitation measures and compromising functional improvement and quality of life. Materials and methods In this case series, platelet-rich fibrin (PRF) was applied to eight wounds from six patients. The patients included had various etiologies (including spinal cord injury, peripheral vascular disease, Guillain-Barré syndrome, and diabetic foot ulcer) with chronic non-healing wounds over different anatomical locations on the body. Pressure ulcer scale for healing (PUSH) score, surface area, and volume of the wounds were evaluated and monitored weekly after PRF dressing. We have applied PRF every week. On average, two PRF dressings were applied, the maximum being three applications. Results The maximum healing rate in terms of PUSH score was observed to be 3.84% per day, and the minimum was 1.19% per day. The maximum healing rate in terms of surface area was observed to be 5.89% per day, and the minimum was 1.78% per day. Three of the wounds showed complete closure. The maximum follow-up period was 10 weeks. The percentage mean Functional Independence Measure (FIM) improvement was calculated to be 15.87% ± 14.04 during the course of hospitalization after PRF application. Conclusion Based on the results, we can conclude that PRF showed accelerated improvement in the healing of chronic non-healing ulcers of various etiologies at different anatomical locations. It has proven to be a safe and effective method, thereby improving their quality of life and functional independence in performing activities of daily living. To our knowledge till date, no other study in a rehabilitation setting has been done on patients having non-healing ulcers due to various etiologies and at different anatomical locations.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Effect of a soft exosuit on daily life gait performance in people with incomplete spinal cord injury: study protocol for a randomized controlled trial.

BACKGROUND: People with incomplete spinal cord injury (iSCI) often have gait impairments that negatively affect daily life gait performance (i.e., ambulation in the home and community setting) and quality of life. They may benefit from light-weight lower extremity exosuits that assist in walking, such as the Myosuit (MyoSwiss AG, Zurich, Switzerland). A previous pilot study showed that participants with various gait disorders increased their gait speed with the Myosuit in a standardized environment. However, the effect of a soft exosuit on daily life gait performance in people with iSCI has not yet been evaluated. OBJECTIVE: The primary study objective is to test the effect of a soft exosuit (Myosuit) on daily life gait performance in people with iSCI. Second, the effect of Myosuit use on gait capacity and the usability of the Myosuit in the home and community setting will be investigated. Finally, short-term impact on both costs and effects will be evaluated. METHODS: This is a two-armed, open label, randomized controlled trial (RCT). Participants will be randomized (1:1) to the intervention group (receiving the Myosuit program) or control group (initially receiving the conventional program). Thirty-four people with chronic iSCI will be included. The Myosuit program consists of five gait training sessions with the Myosuit at the Sint Maartenskliniek. Thereafter, participants will have access to the Myosuit for home use during 6 weeks. The conventional program consists of four gait training sessions, followed by a 6-week home period. After completing the conventional program, participants in the control group will subsequently receive the Myosuit program. The primary outcome is walking time per day as assessed with an activity monitor at baseline and during the first, third, and sixth week of the home periods. Secondary outcomes are gait capacity (10MWT, 6MWT, and SCI-FAP), usability (D-SUS and D-QUEST questionnaires), and costs and effects (EQ-5D-5L). DISCUSSION: This is the first RCT to investigate the effect of the Myosuit on daily life gait performance in people with iSCI. TRIAL REGISTRATION: Clinicaltrials.gov NCT05605912. Registered on November 2, 2022.

Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles inhibit neuronal death after spinal cord injury by regulating the SIRT1/Nrf2/HO-1 pathway.

Background: Oxidative stress and apoptosis of neurons significantly contribute to the pathophysiological cascade of spinal cord injury (SCI). However, the role of hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles (H-sEVs) in promoting SCI repair remains unclear. Hence, the present study aims to investigate the regulatory effects of H-sEVs on neuronal oxidative stress and apoptotic responses following SCI. Methods: The administration of H-sEVs of SCI rats was assessed using behavioral evaluations such as Basso-Beattie-Bresnahan (BBB) scores, neuroelectrophysiological monitoring, and Catwalk gait analysis. Indices of oxidative stress (including superoxide dismutase [SOD], total antioxidant capacity [T-AOC], and malondialdehyde [MDA]) were measured. Neuronal survival was evaluated through Nissl staining, while the expression level of sirtuin 1 (SIRT1) was examined using immunohistochemical staining. Additionally, histological evaluation of lesion size was performed using hematoxylin-eosin (HE) staining. Tunel cell apoptosis staining and analysis of apoptosis-associated proteins (B-cell lymphoma-2 [Bcl2] and BCL2-Associated X [Bax]) were conducted through immunofluorescence staining and western blot, respectively. Furthermore, the model of oxidative stress was established using PC12 cells, and apoptosis levels were assessed via flow cytometry and western blot analysis. Importantly, to ascertain the critical role of SIRT1, we performed SIRT1 knockout experiments in PC12 cells using lentivirus transfection, followed by western blot. Results: Using those behavioral evaluations, we observed significant functional improvement after H-sEVs treatment. Nissl staining revealed that H-sEVs treatment promoted neuronal survival. Moreover, we found that H-sEVs effectively reduced oxidative stress levels after SCI. HE staining demonstrated that H-sEVs could reduce lesion area. Immunohistochemical analysis revealed that H-sEVs enhanced SIRT1 expression. Furthermore, Tunel cell apoptosis staining and western blot analysis of apoptosis-related proteins confirmed the anti-apoptotic effects of H-sEVs. The PC12 cells were used to further substantiate the neuroprotective properties of H-sEVs by significantly inhibiting neuronal death and attenuating oxidative stress. Remarkably, SIRT1 knockout in PC12 cells reversed the antioxidant stress effects induced by H-sEVs treatment. Additionally, we elucidated the involvement of the downstream Nrf2/HO-1 signaling pathway. Conclusion: Our study provides valuable insights into the effects of H-sEVs on neuronal oxidative stress and apoptosis after SCI. These findings underscore the potential clinical significance of H-sEVs-based therapies for SCI.

Periaqueductal gray connectivity in spinal cord injury-induced neuropathic pain.

BACKGROUND AND PURPOSE: Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. METHODS: Ten SCI patients (SCI + NP, n = 7, and SCI - NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI + NP, SCI - NP, and HC). Age and gender were considered as confounding variables. RESULTS: Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI - NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. CONCLUSIONS: Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

Incidence and etiology of traumatic spinal cord injury in Rwanda: a prospective population-based study.

Background: Traumatic spinal cord injury (TSCI) is not only a life-threatening but also life changing event that happens suddenly, the effects extends beyond the TSCI survivors to include their families. In Rwanda to the best knowledge of authors, there is no published information on the epidemiology of TSCI. The aim of this study was therefore to determine the incidence rate, etiology and injury characteristics of TSCI. Methods: All survivors of acute TSCI who met the inclusion criteria were prospectively recruited for a one-year period. The International Spinal Cord Injury Core Data Set was used to collect the minimum set of variables to facilitate worldwide comparison of epidemiological data, while the International Standards for the Neurological Classification was used to categorize TSCI according to the American Spinal Injury Association Impairment Scale (AIS). Data were collected by trained physiotherapists. Study design: A prospective, open-ended, cohort study design. Setting: All referral hospitals within the Republic of Rwanda. Results: Overall, 122 adult individuals sustained a TSCI between 10th October 2019 until 9th October 2020 and all consented to take part in the study. The male-to-female ratio was 3.9:1, and the mean age was 42.5 (SD = ±14.8) years. The crude incidence rate of TSCI was 22.2 per million people (95% CI, 18.4-26.5) with significant differences in sex-adjusted rates for all age groups while men 46 years of age and older presented with the highest incidence. The leading causes of TSCI were falls (73.8%), followed by road traffic accidents (18.9%). Moreover, SCI lesions of the cervical region (n = 69) were the most common, followed by the lumbosacral region (n = 27). Fifty-one (41.8%) participants were diagnosed as complete injury, i.e., AIS A, while incomplete injury category C constituted 35 (28.7%). Conclusion: The incidence and etiology of TSCI in Rwanda are comparable to worldwide estimates and figures. Largely, the etiology of TSCI are preventable as it is caused due to falls and road traffic accidents. There is a need to consider preventive strategies and policies on activities that predispose people to falls. Policies should focus largely on occupational health and safety in both formal and informal sectors of work.

[Research status of lower limb exoskeleton rehabilitation robot].

Lower limb exoskeleton rehabilitation robots are used to improve or restore the walking and movement ability of people with lower limb movement disorders. However, the required functions for patients differ based on various diseases. For example, patients with weak muscle strength require power assistance, patients with spinal cord injuries require motion compensation, patients with gait abnormalities require gait correction, and patients with strokes require neural rehabilitation. To design a more targeted lower limb exoskeleton rehabilitation robot for different diseases, this article summarised and compared existing lower limb exoskeleton rehabilitation robots according to their main functions and the characteristics and rehabilitation needs of various lower limb movement disorders. The correlations between the functions of existing devices and diseases were summarised to provide certain references for the development of new lower limb exoskeleton rehabilitation robots.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury.

BACKGROUND AND OBJECTIVES: Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis-derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. METHODS: Single-cell RNA sequencing (scRNA-seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post-SCI, further focusing on the expression of microglia-related genes for cell sub-clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation-related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time-dependent manner. The expression of glycolysis- and lactylation-related genes was evaluated, as well as the immune infiltration analysis based on the lactylation-related genes. Then, we investigated the bio-effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate-mediated lactylation of microglia-related proteins on SCI. RESULTS: scRNA-seq identified a subcluster of microglia, recombinant chemokine C-X3-C-motif receptor 1+ (CX3CR1+) microglia, which is featured by M1-like phenotype and increased after SCI. KEGG analysis revealed the dysfunctional glycolysis in microglia after SCI surgery, and AUCell analysis suggested that the decreased glycolysis an increased oxidative phosphorylation in CX3CR1+ microglia. Differential gene analysis suggested that several lactylation-related genes (Fabp5, Lgals1, Vim, and Nefl) were downregulated in CX3CR1+ microglia at day 7 after SCI, further validated by the results from bulk RNA sequencing. Immunofluorescence staining indicated the expression of lactate dehydrogenase A (LDHA) in CX3CR1+ microglia also decreased at day 7 after SCI. Cellular experiments demonstrated that the administration of lactate could increase the lactylation level and inhibit the pro-inflammatory phenotype in microglia. Functionally, exercise-mediated lactate production resulted in improved locomotor recovery and decreased inflammatory markers in SCI mice compared to SCI alone. CONCLUSIONS: In the subacute phase of SCI, metabolic remodeling in microglia may be key therapeutic targets to promote nerve regeneration, and lactate contributed to neuroprotection after SCI by influencing microglial lactylation and inflammatory phenotype, which offered a novel approach for therapeutic intervention.

Neglecting Bone Health: A Critical Gap in Management of Muscle Spasticity with Botulinum Toxin in Spinal Cord Injury.

Neuromuscular inhibitors have been quickly advanced from being used only for aesthetic purposes to being used as a treatment for musculoskeletal pain and muscle spasticity. This phenomenon stems from the diminished force exerted by muscles, which are essential for bone remodeling. In this context, it is hypothesized that botulinum toxin (BTX) might exert a direct influence on bone resorption. Although such treatments have the potential to provide patients with significant relief, bone loss occurring due to elective muscle paralysis has yet to be examined in clinical trials. The disuse model resulting from spinal cord injury, characterized by the absence of ground reaction and muscle forces, provides an ideal context for exploring the skeletal ramifications of intramuscular BTX injection. This approach enables an investigation into the intricate interplay between muscle and bone, encompassing the impact of spasticity on bone preservation, the potential positive and negative outcomes of BTX on bone metabolism, and the involvement of the autonomic nervous system in bone remodeling regulation. This paper presents a narrative review of research findings on the disturbance of the typical balance between muscles and bones caused by acute muscle paralysis from BTX, resulting in osteopenia and bone resorption.

The comparative experimental study of rehabilitation program decision for spinal cord injury based on electronic medical records.

Objective: Electronic medical records (EMRs) contain patients' medical and health information. The Utilization of EMRs for assisted diagnosis is of significant importance for the rehabilitation of spinal cord injury (SCI) patients. Therefore, this study proposes a decision-making model for rehabilitation programs of SCI patients based on EMRs. Methods: First, an Electronic Medical Records (EMR) dataset comprising 1252 Spinal Cord Injury (SCI) patients was constructed, and data preprocessing was completed. Second, the Random Forest (RF) feature extraction algorithm was utilized to select case features with high contribution levels. Then, to address the imbalance issue in EMRs, a multi-label learning framework based on the improved MLSMOTE was adopted. Finally, seven multi-label classification models were employed to predict patients' physical therapy (PT) prescriptions. Results: The proposed improved MLSMOTE multi-label learning framework can solve the problem of class imbalance. Compared with the other six models, the CC model has improved significantly in many metrics. Its hamming loss and ranking loss were 0.1388 and 0.2467, and precision, recall, and F1-score were 83.33 %, 81.20 %, and 79.82 % respectively. Conclusions: The improved MLSMOTE multi-label learning framework proposed in this study can make full use of the information in EMRs and effectively improve the decision-making accuracy of rehabilitation treatment programs.