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1.
Heliyon ; 10(16): e36121, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253185

RESUMEN

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.

2.
Heliyon ; 10(16): e36061, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253232

RESUMEN

Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain. Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.

3.
ACS Biomater Sci Eng ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259933

RESUMEN

Traumatic spinal cord injuries (SCI) are debilitating injuries affecting twenty-seven million people worldwide and cause functional impairments. Despite decades of research and medical advancements, current treatment options for SCI remain limited, in part due to the complex pathophysiology of spinal cord lesions including cellular transformation and extracellular matrix (ECM) remodeling. Recent studies have increased focus on fibrotic scarring after SCI, and yet much remains unclear about the impact of fibrotic scarring on SCI lesion progression. Here, using collagen and decellularized spinal cord-based composite hydrogels, a three-dimensional (3D) cell culture model mimicking the fibrous core of spinal cord lesions was implemented to investigate its influence on the surrounding astrocytes. To mimic the fibrotic milieu, collagen fibril thickness was tuned using previously established temperature-controlled casting methods. In our platforms, astrocytes in fibro-mimetic hydrogels exhibited increased levels of activation markers such as glial fibrillary acidic protein and N-cadherin. Furthermore, astrocytes in fibro-mimetic hydrogels deposited more fibronectin and laminin, further hinting that astrocytes may also contribute to fibrotic scarring. These markers were decreased when Rho-ROCK and integrin ß1 were inhibited via pharmacological inhibitors. Mechanistic analysis of Yes-associated protein reveals that blocking integrin ß1 prevents mechanosensing of astrocytes, contributing to altered phenotypes in variable culture conditions. In the presence of these inhibitors, astrocytes increased the secretion of brain-derived neurotrophic factor, and a greater degree of dorsal root ganglia neurite infiltration into the underlying hydrogels was observed. Altogether, this study presents a novel tissue-engineered platform to study fibrotic scarring after SCI and may be a useful platform to advance our understanding of SCI lesion aggravation.

4.
Disabil Rehabil ; : 1-9, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263816

RESUMEN

PURPOSE: Persons with traumatic spinal cord injury (PWTSCI) have expressed a lack of education from healthcare providers and poor shared-decision making between providers and clients. The aim was to explore the healthcare providers' perspective on factors influencing the optimal management of chronic pain. METHODS: Healthcare providers were recruited from two institutions at tertiary healthcare level. Interviews explored current chronic pain management practices, influencing factors and recommendations for improvement. Data saturation occurred after interviewing 11 participants. Thematic analysis was used through a socio-ecological model. RESULTS: The challenges to optimal pain management include appropriate assessment and management of psychological health (intrapersonal level), substance abuse amongst patients (intrapersonal level), access to medication for providers and lack of knowledge by providers (interpersonal and organizational level). To improve chronic pain management, an interdisciplinary team approach should be operationalized at policy and organizational level, monitoring and adjustment of interventions should take place (interpersonal), and family members/caregivers should be involved in the planning and monitoring (interpersonal). CONCLUSION: Factors, at the interpersonal, intrapersonal, organizational and policy levels, influence optimal chronic pain management in the traumatic spinal cord injury (TSCI) population. To mitigate challenges, guidelines for chronic pain management should be developed, particularly for low-resourced developing countries.


Traumatic spinal cord injury chronic painChallenges to effective chronic pain management are multifold and include intrapersonal, interpersonal, organizational, and policy factors, in South Africa.The lack of guidance frameworks and contextualized guidelines inhibits optimal chronic pain management.Holistic assessment and management of chronic pain should be prioritized in the acute care setting in order to follow through to the rehabilitation and primary care settings.Mental health and its impact on chronic pain should be assessed and managed at all levels of care.

5.
J Spinal Cord Med ; : 1-10, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259259

RESUMEN

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.

6.
World J Urol ; 42(1): 519, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259389

RESUMEN

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.


Asunto(s)
Nocturia , Apnea Obstructiva del Sueño , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Nocturia/epidemiología , Nocturia/etiología , Masculino , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Prevalencia , Estudios de Cohortes , Anciano , Presión de las Vías Aéreas Positiva Contínua , Polisomnografía , Urodinámica/fisiología
7.
J Control Release ; 375: 236-248, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39245419

RESUMEN

Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI.

8.
Sci Rep ; 14(1): 20945, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251850

RESUMEN

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.


Asunto(s)
Médula Cervical , Recuperación de la Función , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Médula Cervical/lesiones , Pronóstico , Caminata , Adulto Joven , Adolescente , Resultado del Tratamiento , Suecia/epidemiología , Vértebras Cervicales/lesiones , Vértebras Cervicales/fisiopatología , Anciano de 80 o más Años
9.
J Neurotrauma ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264865

RESUMEN

Spinal cord epidural stimulation (scES) is a therapeutic option that promotes functional improvements in sensory, motor, and autonomic functions following spinal cord injury (SCI). Previous scES mapping studies targeting the lower urinary tract (LUT) in rats demonstrated functional response variability based upon lumbosacral level, parameters used, extent of injury (spinally intact versus chronic anatomically complete spinal transections), and sex. In the current study, female rats with clinically relevant graded incomplete T9 contusion injuries were mapped with scES at 60 days-post-injury at three spinal levels (T13, L3, L6) with a novel miniature 15-electrode array designed to deliver optimal specificity. The results obtained during bladder fill and void cycles conducted under urethane anesthesia indicate frequency dependent sub-motor threshold effects on LUT function with a single row of electrodes positioned across the full medio-lateral extent of the dorsal cord. The findings of improved storage and emptying, represented by significantly longer inter-contractile intervals with T13 scES and L3 scES and by a significantly increased estimated void efficiency with L6 scES, respectively, is consistent with previous studies using intact and chronic complete transected male and female rats. The data support the efficacy of selective spinal network stimulation to drive functionally relevant networks for storage versus emptying phases of the urinary cycle. The current findings further demonstrate the translational promise of scES for SCI individuals with LUT dysfunctions, regardless of injury severity.

10.
Br Med Bull ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39222962

RESUMEN

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.

12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 833-839, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39218611

RESUMEN

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.


Asunto(s)
Dispositivo Exoesqueleto , Extremidad Inferior , Robótica , Traumatismos de la Médula Espinal , Rehabilitación de Accidente Cerebrovascular , Humanos , Extremidad Inferior/fisiopatología , Robótica/instrumentación , Traumatismos de la Médula Espinal/rehabilitación , Rehabilitación de Accidente Cerebrovascular/instrumentación , Rehabilitación de Accidente Cerebrovascular/métodos , Marcha/fisiología , Trastornos del Movimiento/rehabilitación , Caminata
13.
CNS Neurosci Ther ; 30(9): e70028, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39218784

RESUMEN

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.


Asunto(s)
Ácido Láctico , Ratones Endogámicos C57BL , Microglía , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratones , Masculino , Ácido Láctico/metabolismo , Análisis de Secuencia de ARN/métodos , Fármacos Neuroprotectores/farmacología , Glucólisis/efectos de los fármacos , Glucólisis/fisiología
14.
J Musculoskelet Neuronal Interact ; 24(3): 318-324, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39219330

RESUMEN

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.


Asunto(s)
Toxinas Botulínicas , Espasticidad Muscular , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Toxinas Botulínicas/administración & dosificación , Toxinas Botulínicas/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Animales , Huesos/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Resorción Ósea , Músculo Esquelético/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológico
15.
Mol Neurobiol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230866

RESUMEN

Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.

16.
J Orthop Translat ; 48: 133-145, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39220679

RESUMEN

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.

17.
J Rehabil Assist Technol Eng ; 11: 20556683241278306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39221173

RESUMEN

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.

18.
Mater Today Bio ; 28: 101218, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39221206

RESUMEN

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.

19.
Mol Pharm ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235393

RESUMEN

Spinal cord injury (SCI) is a highly disabling neurological disorder. Its pathological process comprises an initial acute injury phase (primary injury) and a secondary injury phase (subsequent chronic injury). Although surgical, drug, and cell therapies have made some progress in treating SCI, there is no exact therapeutic strategy for treating SCI and promoting nerve regeneration due to the complexity of the pathological SCI process. The development of novel drug delivery systems to treat SCI is expected to significantly impact the individualized treatment of SCI due to its unique and excellent properties, such as active targeting and controlled release. In this review, we first describe the pathological progression of the SCI response, including primary and secondary injuries. Next, we provide a concise overview of newly developed nanoplatforms and their potential application in regulating and treating different pathological processes of SCI. Then, we introduce the existing potential problems and future clinical application perspectives of biomedical engineering-based therapies for SCI.

20.
Adv Sci (Weinh) ; : e2405759, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225315

RESUMEN

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.

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