RESUMO
Spinal cord injury (SCI) results in significant neural damage and inhibition of axonal regeneration due to an imbalanced microenvironment. Extensive evidence supports the efficacy of mesenchymal stem cell (MSC) transplantation as a therapeutic approach for SCI. This review aims to present an overview of MSC regulation on the imbalanced microenvironment following SCI, specifically focusing on inflammation, neurotrophy and axonal regeneration. The application, limitations and future prospects of MSC transplantation are discussed as well. Generally, a comprehensive perspective is provided for the clinical translation of MSC transplantation for SCI.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Células-Tronco Mesenquimais/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Microambiente Celular , Regeneração NervosaRESUMO
Traumatic spinal cord injury is characterized by immediate and irreversible tissue loss at the lesion site and secondary tissue damage. Secondary injuries should, in principle, be preventable, although no effective treatment options currently exist for patients with acute spinal cord injury. Traumatized tissues release excessive amounts of adenosine triphosphate and activate the P2X purinoceptor 7/pannexin1 complex, which is associated with secondary injury. We investigated the neuroprotective effects of the blue dye Brilliant Blue FCF, a selective inhibitor of P2X purinoceptor 7/pannexin1 that is approved for use as a food coloring, by comparing it with Brilliant Blue G, a P2X7 purinoceptor antagonist, and carbenoxolone, which attenuates P2X purinoceptor 7/pannexin1 function, in a rat spinal cord injury model. Brilliant Blue FCF administered early after spinal cord injury reduced spinal cord anatomical damage and improved motor recovery without apparent toxicity. Brilliant Blue G had the highest effect on this neurological recovery, with Brilliant Blue FCF and carbenoxolone having comparable improvement. Furthermore, Brilliant Blue FCF administration reduced local astrocytic and microglial activation and neutrophil infiltration, and no differences in these histological effects were observed between compounds. Thus, Brilliant Blue FCF protects spinal cord neurons after spinal cord injury and suppresses local inflammatory responses as well as Brilliant Blue G and carbenoxolone.
Assuntos
Trifosfato de Adenosina , Carbenoxolona , Conexinas , Proteínas do Tecido Nervoso , Recuperação de Função Fisiológica , Corantes de Rosanilina , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Animais , Conexinas/metabolismo , Conexinas/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Carbenoxolona/farmacologia , Carbenoxolona/uso terapêutico , Corantes de Rosanilina/farmacologia , Corantes de Rosanilina/uso terapêutico , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Recuperação de Função Fisiológica/efeitos dos fármacos , Ratos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Ratos Sprague-Dawley , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/efeitos dos fármacos , Feminino , Infiltração de Neutrófilos/efeitos dos fármacosRESUMO
INTRODUCTION: Spinal cord injury is one of the common injury which causes damage to the spinal cord due to trauma, diseases or degenerations leading to disability and decreasing life expectancy. The study aims to find the characteristics of spinal cord injury presenting at a tertiary care centre. METHODS: A Descriptive hospital based cross-sectional study was conducted at Pokhara, Gandaki Province, from 28th March to 25th September, 2023. 139 participants were interviewed for the study. Structured interview schedule and validated questionnaires were used for data collection. Ethical approval was taken for the study (Reference number: 151/079). RESULTS: A total of 139 cases were observed; most common affected age group was between 25-55 years with a mean age of 48.68 years. Most (66.9%) of the spinal cord injury patients were not enrolled in health insurance program. Most 107 (77.0%) common cause for spinal cord injury was falls from height. Age, gender, occupation and duration of stay in the hospital were statistically significant with mode of treatment. CONCLUSIONS: Spinal cord injury mostly traumatic commonly due to fall from height affecting mainly male population residing in rural areas at their fourth decade of life who are mainly involve in manual work and agriculture. Spinal cord injury is a major health problem at global and local level causing major morbidity.
Assuntos
Traumatismos da Medula Espinal , Centros de Atenção Terciária , Humanos , Nepal/epidemiologia , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem , Acidentes por Quedas/estatística & dados numéricos , Idoso , Tempo de Internação/estatística & dados numéricos , Adolescente , Seguro Saúde/estatística & dados numéricosRESUMO
STUDY DESIGN: Longitudinal observational study. Measurements were undertaken between weeks 4-6 post-spinal cord injury (SCI), repeated at week 8 and every 4 weeks thereafter until week 20 or rehabilitation discharge, whichever occurred first. OBJECTIVES: Observe variation in measured resting energy expenditure (REE) and body composition in males undergoing SCI rehabilitation, compare REE with SCI-specific prediction equations incorporating fat-free mass (FFM), and explore the prevalence of clinical factors that may influence individual REE. SETTING: Spinal Injuries Unit, Brisbane, Queensland, Australia. METHODS: Indirect calorimetry was used to measure REE and bioimpedance spectroscopy to assess body composition. Four SCI-specific FFM-based REE and basal metabolic rate (BMR) prediction equations were compared to measured REE. A clinically significant change in REE was defined as +/- 10% difference from the week 4-6 measurement. Clinical factors that may affect REE variations were collected including infection, pressure injuries, autonomic dysreflexia, spasticity, and medications. RESULTS: Fifteen people participated (mean age 35 ± 13 years, 67% paraplegic). There was no statistically significant change in mean REE, weight, or body composition, and the Chun and Nightingale BMR prediction equations performed best (rc > 0.8 at all time points). One-third of participants had >10% change in REE on 11 occasions, with clinical factors not consistently associated with the observed changes. CONCLUSION: During SCI rehabilitation, mean REE, weight, and body composition remain unchanged, and FFM-based BMR prediction equations may be an acceptable alternative to indirect calorimetry. Future research designs should avoid single indirect calorimetry measures as snapshot data may not represent typical REE in this population.
Assuntos
Composição Corporal , Calorimetria Indireta , Metabolismo Energético , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Masculino , Adulto , Projetos Piloto , Metabolismo Energético/fisiologia , Composição Corporal/fisiologia , Pessoa de Meia-Idade , Estudos Longitudinais , Metabolismo Basal/fisiologia , Adulto Jovem , Descanso/fisiologiaRESUMO
In persons with a spinal cord injury (SCI), resistance training using neuromuscular electrical stimulation (NMES-RT) increases lean mass in the lower limbs. However, whether protein supplementation in conjunction with NMES-RT further enhances this training effect is unknown. In this randomized controlled pilot trial, 15 individuals with chronic SCI engaged in 3 times/week NMES-RT, with (NMES+PRO, n = 8) or without protein supplementation (NMES, n = 7), for 12 weeks. Before and after the intervention, whole body and regional body composition (DXA) and fasting glucose and insulin concentrations were assessed in plasma. Adherence to the intervention components was ≥96%. Thigh lean mass was increased to a greater extent after NMES+PRO compared to NMES (0.3 (0.2, 0.4) kg; p < 0.001). Furthermore, fasting insulin concentration and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were decreased similarly in both groups (fasting insulin: 1 [-9, 11] pmolâL-1; HOMA-IR: 0.1 [-0.3, 0.5] AU; both p ≥ 0.617). Twelve weeks of home-based NMES-RT increased thigh lean mass, an effect that was potentiated by protein supplementation. In combination with the excellent adherence and apparent improvement in cardiometabolic health outcomes, these findings support further investigation through a full-scale randomized controlled trial.
Assuntos
Composição Corporal , Terapia por Estimulação Elétrica , Treinamento Resistido , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Masculino , Treinamento Resistido/métodos , Feminino , Adulto , Projetos Piloto , Terapia por Estimulação Elétrica/métodos , Pessoa de Meia-Idade , Suplementos Nutricionais , Resistência à Insulina , Insulina/sangue , Proteínas Alimentares/administração & dosagem , Glicemia/metabolismo , Músculo Esquelético/metabolismoRESUMO
Objective: To identify factors impacting survivorship among people living with spinal cord injury (SCI) and volunteering in a peer mentorship program. Research Method/Design: Semi-structured interviews were conducted by a leader of a non-profit organization designed to promote independent living after SCI. Questions explored intrinsic factors such as resilience and emotional coping as well extrinsic factors such as family support and accessibility challenges that impacted their SCI survivorship journey. Two independent anonymous reviewers conducted thematic analysis to identify these factors. Results: Twenty-eight members of the SCI peer mentorship program participated. Four themes affecting survivorship were identified: Sense of Achievement, Post-Injury Growth, Post-Injury Challenges, and Giving and Receiving Support. Nearly all participants focused their responses on Post-Injury Growth and Giving and Receiving Support as reasons for their interest in serving as peer mentors. Conclusions: This study highlights a need for peer community integration following SCI and underscores the importance of using a community-driven participatory model to inform and guide research. Peer mentorship programs can link SCI survivors to mentors and facilitate other sources of social fulfillment and thus can have a profound impact on individuals' survivorship post-SCI. This study identified a Sense of Achievement, Post-Injury Growth, Giving and Receiving Support, and Post-Injury Challenges as factors that most impact the SCI survivorship journey. This community leader's work underscores the importance of cognitive framing and social networks in post-injury rehabilitation in this population. Future directions include analyzing the longitudinal effects of peer mentorship participation on life satisfaction and community building in individuals living with SCI.
Assuntos
Mentores , Grupo Associado , Pesquisa Qualitativa , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Sobrevivência , Idoso , Adaptação Psicológica , Apoio SocialRESUMO
Exercise training is a conventional treatment strategy throughout the entire treatment process for patients with spinal cord injury (SCI). Currently, exercise modalities for SCI patients primarily include aerobic exercise, endurance training, strength training, high-intensity interval training, and mind-body exercises. These exercises play a positive role in enhancing skeletal muscle function, inducing neuroprotection and regeneration, thereby influencing neural plasticity, reducing limb spasticity, and improving motor function and daily living abilities in SCI patients. However, the mechanism by which exercise training promotes functional recovery after SCI is still unclear, and there is no consensus on a unified and standardized exercise treatment plan. Different exercise methods may bring different benefits. After SCI, patients' physical activity levels decrease significantly due to factors such as motor dysfunction, which may be a key factor affecting changes in exerkines. The changes in exerkines of SCI patients caused by exercise training are an important and highly relevant and visual evaluation index, which may provide a new research direction for revealing the intrinsic mechanism by which exercise promotes functional recovery after SCI. Therefore, this article summarizes the changes in the expression of common exerkines (neurotrophic factors, inflammatory factors, myokines, bioactive peptides) after SCI, and intends to analyze the impact and role of different exercise methods on functional recovery after SCI from the perspective of exerkines mechanism. We hope to provide theoretical basis and data support for scientific exercise treatment programs after SCI.
Assuntos
Terapia por Exercício , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Humanos , Animais , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Recuperação de Função Fisiológica/fisiologiaRESUMO
Background: spinal cord injury leaves as a sequel in the acute and chronic period, deficiencies in the stability of joint functions and in the function of voluntary movement control. Those with good trunk control have a greater probability of carrying out activities of daily living by themselves; up to now, we do not have reliable tools in Argentina that evaluate trunk control in these subjects. Objectives: to cross-culturally adapt the trunk control test to Argentinean Spanish in subjects with sequelae of spinal cord injury and to establish interobserver and intraobserver reliability. Methodology: the subjects were admitted using a non-probabilistic convenience sampling. Subjects who were between 15 and 75 years old and had a diagnosis of spinal cord injury were included. Subjects who had: another neurological diagnosis, alteration in sensory organs, conditions that prevent the performance of the test, and psychiatric illness were excluded. Results: 30 subjects were included for cross-cultural adaptation and 55 for reliability. Semantic modifications were made to all items and response options. The intraobserver and interobserver reliability of the scale or subdomains did not achieve a sufficient score. Conclusion: the trunk control test was adapted cross-culturally to Argentine Spanish and interobserver and intraobserver reliability was established. The adaptation was achieved through semantic changes and the reliability was not sufficient. In the future, studies should be carried out to improve the reliability and study the validity of the tool.
Introducción: la lesión de la médula espinal deja como secuela en el período agudo y crónico, deficiencias en la estabilidad de las funciones articulares y de la función del control de los movimientos voluntarios. Aquellos con buen control de tronco poseen una mayor probabilidad de realizar por sí mismos actividades de la vida diaria, hasta el momento, no contamos en Argentina con herramientas fiables que evalúen el control de tronco en estos sujetos. Objetivos: adaptar transculturalmente al castellano argentino el trunk control test en sujetos con secuela de lesión medular espinal y establecer la fiabilidad interobservador, intraobservador. Metodología: los sujetos fueron ingresados mediante un muestreo no probabilístico por conveniencia. Se incluyeron sujetos que: posean entre 15 años a 75 años y tengan diagnóstico de lesión medular espinal, se excluyeron sujetos que posean: otro diagnóstico neurológico, alteración en los órganos sensoriales, condiciones que impidan la realización de la prueba y enfermedad psiquiátrica. Resultados: 30 sujetos fueron incluidos para la adaptación transcultural y 55 para la fiabilidad. Se realizaron modificaciones semánticas en todos los ítems y opciones de respuesta. La fiabilidad intraobservador e interobservador de la escala o de los subdominios no logró un puntaje suficiente. Conclusión: se adaptó transculturalmente al castellano argentino el trunk control test y se estableció la fiabilidad interobservador, intraobservador. La adaptación se logró a través de cambios semánticos y la fiabilidad no fue suficiente. A futuro se deberán realizar estudios para mejorar la fiabilidad y estudiar la validez de la herramienta.
Assuntos
Traumatismos da Medula Espinal , Traduções , Humanos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Argentina , Adulto , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Feminino , Masculino , Adolescente , Idoso , Adulto Jovem , Comparação Transcultural , Variações Dependentes do Observador , Tronco/fisiopatologia , Avaliação da Deficiência , Inquéritos e Questionários/normas , Atividades CotidianasRESUMO
BACKGROUND: A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study. OBJECTIVE: This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI). METHODS: iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining. RESULTS: The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration. CONCLUSION: These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.
Assuntos
Exossomos , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Traumatismos da Medula Espinal , Exossomos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Animais , MicroRNAs/genética , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Camundongos , Modelos Animais de Doenças , Neurônios/metabolismo , Bioengenharia/métodos , Feminino , Regeneração da Medula Espinal , HumanosRESUMO
BACKGROUND: Spinal cord injury (SCI) results in severe, permanent functional changes and has become a global health priority due to its high incidence, cost, and disability rate. Current national epidemiological data on SCI in China are limited and outdated. This study aimed to provide a comprehensive, national cross-sectional investigation of SCI epidemiology in China. METHODS: This cross-sectional study included 3055 SCI participants aged 8 to 78 years, conducted from May to September 2023. Data collected encompassed demographic characteristics, employment status, etiology, years lived with disability (YLD), family structure, caregiving status, income, health insurance, paralysis type, and health-related quality of life (HRQoL). Descriptive statistics analyses were used to assess demographic and injury characteristics. Group differences were assessed using t-tests, one-way ANOVA and Chi-square tests. Significant factors were examined using multivariate regression analysis. RESULTS: The majority (88.9%) of respondents were aged 15 to 59 years, with a male-to-female ratio of 2.36:1. Car accidents caused 45.4% of tetraplegia cases, falls caused 35.9% of paraplegia cases, and myelitis was the leading cause of non-traumatic SCI. Among paraplegia participants, 65.5% had complete SCI, while 53.1% of tetraplegia participants had incomplete SCI. Functional improvement was reported by 9.58% of participants. Half (50.3%) of the respondents were unemployed, and 75% had incomes below the national average. HRQoL was significantly lower in the SCI population compared to controls, mainly influenced by injury site, income, age and etiology (p < 0.05). CONCLUSIONS: SCI participants in China exhibit low HRQoL and reemployment rates. Accessible community and vocational rehabilitation programs, alongside robust public medical services, are essential for enhancing reemployment and HRQoL among SCI participants, reducing the overall disease burden.
Assuntos
Qualidade de Vida , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/psicologia , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Adolescente , Adulto Jovem , Idoso , Criança , Paraplegia/reabilitação , Paraplegia/epidemiologia , Paraplegia/psicologiaRESUMO
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.
Assuntos
Noctúria , Apneia Obstrutiva do Sono , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Noctúria/epidemiologia , Noctúria/etiologia , Masculino , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Prevalência , Estudos de Coortes , Idoso , Pressão Positiva Contínua nas Vias Aéreas , Polissonografia , Urodinâmica/fisiologiaRESUMO
This retrospective study analyzed prognostic factors for neurological improvement and ambulation in 194 adult patients (≥ 15 years) with traumatic cervical spinal cord injuries treated at the neurological SCI unit (SCIU) at the Karolinska University Hospital Stockholm, Sweden, between 2010 and 2020. The primary outcome was American spinal injury association impairment scale (AIS) improvement, with secondary focus on ambulation restoration. Results showed 41% experienced AIS improvement, with 51% regaining ambulation over a median follow-up of 3.7 years. Significant AIS improvement (p < 0.001) and reduced bladder/bowel dysfunction (p < 0.001) were noted. Multivariable analysis identified initial AIS C-D (< 0.001), central cord syndrome (p = 0.016), and C0-C3 injury (p = 0.017) as positive AIS improvement predictors, while lower extremity motor score (LEMS) (p < 0.001) and longer ICU stays (p < 0.001) were negative predictors. Patients with initial AIS C-D (p < 0.001) and higher LEMS (p < 0.001) were more likely to regain ambulation. Finally, older age was a negative prognostic factor (p = 0.003). In conclusion, initial injury severity significantly predicted neurological improvement and ambulation. Recovery was observed even in severe cases, emphasizing the importance of tailored rehabilitation for improved outcomes.
Assuntos
Medula Cervical , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Medula Cervical/lesões , Prognóstico , Caminhada , Adulto Jovem , Adolescente , Resultado do Tratamento , Suécia/epidemiologia , Vértebras Cervicais/lesões , Vértebras Cervicais/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
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.
Assuntos
Marcha , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/reabilitação , Resultado do Tratamento , Fatores de Tempo , Exoesqueleto Energizado , Qualidade de Vida , Recuperação de Função Fisiológica , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/fisiopatologia , Fenômenos Biomecânicos , Atividades Cotidianas , Análise Custo-Benefício , Feminino , Adulto , Masculino , Desenho de Equipamento , Custos de Cuidados de Saúde , Pessoa de Meia-IdadeRESUMO
Rationale: Spinal cord injury (SCI)-induced vascular damage causes ischemia and hypoxia at the injury site, which, in turn, leads to profound metabolic disruptions. The effects of these metabolic alterations on neural tissue remodeling and functional recovery have yet to be elucidated. The current study aimed to investigate the consequences of the SCI-induced hypoxic environment at the epicenter of the injury. Methods: This study employed metabolomics to assess changes in energy metabolism after SCI. The use of a lactate sensor identified lactate shuttle between endothelial cells (ECs) and neurons. Reanalysis of single-cell RNA sequencing data demonstrated reduced MCT1 expression in ECs after SCI. Additionally, an adeno-associated virus (AAV) overexpressing MCT1 was utilized to elucidate its role in endothelial-neuronal interactions, tissue repair, and functional recovery. Results: The findings revealed markedly decreased monocarboxylate transporter 1 (MCT1) expression that facilitates lactate delivery to neurons to support their energy metabolism in ECs post-SCI. This decreased expression of MCT1 disrupts lactate transport to neurons, resulting in a metabolic imbalance that impedes axonal regeneration. Strikingly, our results suggested that administering adeno-associated virus specifically to ECs to restore MCT1 expression enhances axonal regeneration and improves functional recovery in SCI mice. These findings indicate a novel link between lactate shuttling from endothelial cells to neurons following SCI and subsequent neural functional recovery. Conclusion: In summary, the current study highlights a novel metabolic pathway for therapeutic interventions in the treatment of SCI. Additionally, our findings indicate the potential benefits of targeting lactate transport mechanisms in recovery from SCI.
Assuntos
Axônios , Células Endoteliais , Ácido Láctico , Transportadores de Ácidos Monocarboxílicos , Traumatismos da Medula Espinal , Simportadores , Traumatismos da Medula Espinal/metabolismo , Animais , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Células Endoteliais/metabolismo , Ácido Láctico/metabolismo , Camundongos , Axônios/metabolismo , Simportadores/metabolismo , Simportadores/genética , Recuperação de Função Fisiológica/fisiologia , Dependovirus/genética , Regeneração Nervosa , Neurônios/metabolismo , Metabolismo Energético , Camundongos Endogâmicos C57BL , Feminino , Modelos Animais de Doenças , HumanosRESUMO
AIMS: Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects. MATERIALS AND METHODS: In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up. RESULTS: The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs. CONCLUSION: In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.
Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Transplante Homólogo , Animais , Cães , Traumatismos da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/terapia , Transplante Homólogo/métodos , Fusão Vertebral/métodos , Potencial Evocado Motor/fisiologia , Potencial Evocado Motor/efeitos dos fármacos , Masculino , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Feminino , Recuperação de Função Fisiológica/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Imunossupressores/uso terapêutico , Imunossupressores/farmacologia , Metilprednisolona/uso terapêuticoRESUMO
BACKGROUND: Spinal cord injury (SCI) often leads to a loss of motor and sensory function. Axon regeneration and outgrowth are key events for functional recovery after spinal cord injury. Endogenous growth of axons is associated with a variety of factors. Inspired by the relationship between developing nerves and blood vessels, we believe spinal cord-derived microvascular endothelial cells (SCMECs) play an important role in axon growth. RESULTS: We found SCMECs could promote axon growth when co-cultured with neurons in direct and indirect co-culture systems via downregulating the miR-323-5p expression of neurons. In rats with spinal cord injury, neuron-targeting nanoparticles were employed to regulate miR-323-5p expression in residual neurons and promote function recovery. CONCLUSIONS: Our study suggests that SCMEC can promote axon outgrowth by downregulating miR-323-5p expression within neurons, and miR-323-5p could be selected as a potential target for spinal cord injury repair.
Assuntos
Axônios , Técnicas de Cocultura , Células Endoteliais , MicroRNAs , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Medula Espinal , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Células Endoteliais/metabolismo , Ratos , Medula Espinal/metabolismo , Axônios/metabolismo , Neurônios/metabolismo , Células Cultivadas , Nanopartículas/química , Regeneração Nervosa , FemininoRESUMO
Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of CD11b mRNA starting from 1 d after injury, which persisted up to 28 d. CD11b knockout (KO) mice and their wildtype littermates were subjected to moderate SCI. At 1 d post-injury, qPCR showed increased expression of genes involved with inflammation-resolving processes in CD11b KO mice. Flow cytometry analysis of CD45intLy6C-CX3CR1+ microglia, CD45hiLy6C+Ly6G- monocytes, and CD45hiLy6C+Ly6G+ neutrophils revealed significantly reduced cell counts as well as reactive oxygen species (ROS) production in CD11b KO mice at d3 post-injury. Further examination with NanoString and RNA-seq showed upregulation of pro-inflammatory genes, but downregulation of the ROS pathway. Importantly, CD11b KO mice exhibited significantly improved locomotor function, reduced cutaneous mechanical/thermal hypersensitivity, and limited tissue damage at 8 weeks post-injury. Collectively, our data suggest an important role for CD11b in regulating tissue inflammation and functional outcome following SCI.
Assuntos
Antígeno CD11b , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Feminino , Camundongos , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Inflamação/patologia , Antígeno de Macrófago 1/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Microglia/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/genéticaRESUMO
Individuals with spinal cord injury (SCI) experience a notable decrease in bone mass below the level of injury. While studies have primarily focused on the acute phase with a small cohort, this study aimed to provide comprehensive insights into bone loss patterns over time. A total of 427 individuals with SCI who underwent dual-energy X-ray absorptiometry (DXA) testing at the Korea National Rehabilitation Center (2010-2021) were included and analyzed by categorizing the DXA results into 1-year intervals based on postinjury duration. Demographic characteristics (age, sex, body mass index, and alcohol/smoking history) and SCI-related factors (etiology, severity, extent of injury, motor score, and Korean Spinal Cord Independence Measure 3rd edition) were collected and analyzed. Linear mixed models and Bonferroni post hoc tests were performed to assess temporal changes in bone mass and linear regression analysis to assess the associations between possible risk factors and bone loss. DXA results revealed that substantial annual bone loss occurred in the total hip site up to 3 years postinjury and in the femoral neck site up to 2 years postinjury. Old age, women, and low body mass index were significant risk factors for bone loss in the SCI population. Additionally, during the chronic phase, lower Korean Spinal Cord Independence Measure 3rd edition scores were associated with low bone mass. Significant annual bone loss in the hip region persists for up to 3 years postinjury in individuals with SCI. While prioritizing the risk factors for osteoporosis commonly used in the general population, applying the SCIM score in the chronic phase may provide additional information on bone loss risk.