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1.
Spinal Cord Ser Cases ; 10(1): 21, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615029

RESUMO

STUDY DESIGN: Scoping systematic review. OBJECTIVES: To summarize the available experimental clinical and animal studies for the identification of all CSF and serum-derived biochemical markers in human and rat SCI models. SETTING: Tehran, Iran. METHODS: In this scoping article, we systematically reviewed the electronic databases of PubMed, Scopus, WOS, and CENTRAL to retrieve current literature assessing the levels of different biomarkers in human and rat SCI models. RESULTS: A total of 19,589 articles were retrieved and 6897 duplicated titles were removed. The remaining 12,692 studies were screened by their title/abstract and 12,636 were removed. The remaining 56 were considered for full-text assessment, and 11 papers did not meet the criteria, and finally, 45 studies were included. 26 studies were human observational studies comprising 1630 patients, and 19 articles studied SCI models in rats, including 832 rats. Upon reviewing the literature, we encountered a remarkable heterogeneity in terms of selected biomarkers, timing, and method of measurement, studied models, extent, and mechanism of injury as well as outcome assessment measures. CONCLUSIONS: The specific expression and distribution patterns of biomarkers in relation to spinal cord injury (SCI) phases, and their varied concentrations over time, suggest that cerebrospinal fluid (CSF) and blood biomarkers are effective measures for assessing the severity of SCI.


Assuntos
Traumatismos da Medula Espinal , Animais , Humanos , Ratos , Irã (Geográfico) , Biomarcadores , Bases de Dados Factuais , Avaliação de Resultados em Cuidados de Saúde
2.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612590

RESUMO

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings. Notably, the training facilitates the preservation of spinal cord tissue, effectively reducing secondary damage and promoting the maintenance of neural fibers in the injured area. A key finding is the significant stimulation of axonal growth around the injury epicenter in trained rats, marked by increased growth-associated protein 43 (GAP43) expression. Despite these advancements, the study notes a limited impact of treadmill training on motoneuron adaptation and highlights minimal changes in the astrocyte and neuron-glial antigen 2 (NG2) response. This suggests that, while treadmill training is instrumental in functional improvements post-SCI, its influence on certain neural cell types and glial populations is constrained.


Assuntos
Astrócitos , Traumatismos da Medula Espinal , Animais , Ratos , Humanos , Neuroglia , Eletromiografia , Neurônios Motores , Traumatismos da Medula Espinal/terapia , Axônios
3.
Cells ; 13(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38607008

RESUMO

PURPOSE OF THIS REVIEW: Manipulating or re-engineering the damaged human spinal cord to achieve neuro-recovery is one of the foremost challenges of modern science. Addressing the restricted permission of neural cells and topographically organised neural tissue for self-renewal and spontaneous regeneration, respectively, is not straightforward, as exemplified by rare instances of translational success. This review assembles an understanding of advances in nanomedicine for spinal cord injury (SCI) and related clinical indications of relevance to attempts to design, engineer, and target nanotechnologies to multiple molecular networks. RECENT FINDINGS: Recent research provides a new understanding of the health benefits and regulatory landscape of nanomedicines based on a background of advances in mRNA-based nanocarrier vaccines and quantum dot-based optical imaging. In relation to spinal cord pathology, the extant literature details promising advances in nanoneuropharmacology and regenerative medicine that inform the present understanding of the nanoparticle (NP) biocompatibility-neurotoxicity relationship. In this review, the conceptual bases of nanotechnology and nanomaterial chemistry covering organic and inorganic particles of sizes generally less than 100 nm in diameter will be addressed. Regarding the centrally active nanotechnologies selected for this review, attention is paid to NP physico-chemistry, functionalisation, delivery, biocompatibility, biodistribution, toxicology, and key molecular targets and biological effects intrinsic to and beyond the spinal cord parenchyma. SUMMARY: The advance of nanotechnologies for the treatment of refractory spinal cord pathologies requires an in-depth understanding of neurobiological and topographical principles and a consideration of additional complexities involving the research's translational and regulatory landscapes.


Assuntos
Nanomedicina , Traumatismos da Medula Espinal , Humanos , Distribuição Tecidual , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Medicina Regenerativa
4.
Cells ; 13(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38607020

RESUMO

Spinal cord injury (SCI) leads to significant functional impairments below the level of the injury, and astrocytes play a crucial role in the pathophysiology of SCI. Astrocytes undergo changes and form a glial scar after SCI, which has traditionally been viewed as a barrier to axonal regeneration and functional recovery. Astrocytes activate intracellular signaling pathways, including nuclear factor κB (NF-κB) and Janus kinase-signal transducers and activators of transcription (JAK/STAT), in response to external stimuli. NF-κB and STAT3 are transcription factors that play a pivotal role in initiating gene expression related to astrogliosis. The JAK/STAT signaling pathway is essential for managing secondary damage and facilitating recovery processes post-SCI: inflammation, glial scar formation, and astrocyte survival. NF-κB activation in astrocytes leads to the production of pro-inflammatory factors by astrocytes. NF-κB and STAT3 signaling pathways are interconnected: NF-κB activation in astrocytes leads to the release of interleukin-6 (IL-6), which interacts with the IL-6 receptor and initiates STAT3 activation. By modulating astrocyte responses, these pathways offer promising avenues for enhancing recovery outcomes, illustrating the crucial need for further investigation into their mechanisms and therapeutic applications in SCI treatment.


Assuntos
NF-kappa B , Traumatismos da Medula Espinal , Humanos , NF-kappa B/metabolismo , Astrócitos/metabolismo , Doenças Neuroinflamatórias , Janus Quinases/metabolismo , Gliose/complicações , Transdução de Sinais/fisiologia , Traumatismos da Medula Espinal/terapia
5.
Cells ; 13(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38607084

RESUMO

Subacute spinal cord injury (SCI) displays a complex pathophysiology associated with pro-inflammation and ensuing tissue damage. Microglia, the resident innate immune cells of the CNS, in concert with infiltrating macrophages, are the primary contributors to SCI-induced inflammation. However, subpopulations of activated microglia can also possess immunomodulatory activities that are essential for tissue remodeling and repair, including the production of anti-inflammatory cytokines and growth factors that are vital for SCI recovery. Recently, reports have provided convincing evidence that sex-dependent differences exist in how microglia function during CNS pathologies and the extent to which these cells contribute to neurorepair and endogenous recovery. Herein we employed flow cytometry and immunohistochemical methods to characterize the phenotype and population dynamics of activated innate immune cells within the injured spinal cord of age-matched male and female rats within the first week (7 days) following thoracic SCI contusion. This assessment included the analysis of pro- and anti-inflammatory markers, as well as the expression of critical immunomodulatory kinases, including P38 MAPK, and transcription factors, such as NFκB, which play pivotal roles in injury-induced inflammation. We demonstrate that activated microglia from the injured spinal cord of female rats exhibited a significantly diminutive pro-inflammatory response, but enhanced anti-inflammatory activity compared to males. These changes included lower levels of iNOS and TLR4 expression but increased levels of ARG-1 and CD68 in females after SCI. The altered expression of these markers is indicative of a disparate secretome between the microglia of males and females after SCI and that the female microglia possesses higher phagocytic capabilities (increased CD68). The examination of immunoregulatory kinases and transcription factors revealed that female microglia had higher levels of phosphorylated P38Thr180/Tyr182 MAPK and nuclear NFκB pp50Ser337 but lower amounts of nuclear NFκB pp65Ser536, suggestive of an attenuated pro-inflammatory phenotype in females compared to males after SCI. Collectively, this work provides novel insight into some of the sex disparities that exist in the innate immune response after SCI and indicates that sex is an important variable when designing and testing new therapeutic interventions or interpretating positive or negative responses to an intervention.


Assuntos
Traumatismos da Medula Espinal , Ratos , Animais , Masculino , Feminino , Traumatismos da Medula Espinal/patologia , Imunidade Inata , Inflamação/patologia , Anti-Inflamatórios , Fatores de Transcrição
6.
Urol Clin North Am ; 51(2): 163-176, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609189

RESUMO

The Neurogenic Bladder Research Group (NBRG) was formed with the mission to optimize quality of life (QoL), surgical outcomes, and clinical care of patients with neurogenic lower urinary tract dysfunction. One of the original priorities of the organization was to support creation of the NBRG Spinal Cord Injury (SCI) Registry. The aim of this Registry was to establish a prospective database, in order to study bladder-related QoL after SCI. The study enrolled close to 1500 participants from across North America over an 18 month time-period (January 2016-July 2017).


Assuntos
Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Humanos , Bexiga Urinária , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/terapia , Qualidade de Vida , Sistema de Registros
7.
Urol Clin North Am ; 51(2): 277-284, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609199

RESUMO

Individual and social factors are important for clinical decision-making in patients with neurogenic bladder secondary to spinal cord injury (SCI). These factors include the availability of caregivers, social infrastructure, and personal preferences, which all can drive bladder management decisions. These elements can be overlooked in clinical decision-making; therefore, there is a need to elicit and prioritize patient preferences and values into neurogenic bladder care to facilitate personalized bladder management choices. For the purposes of this article, we review the role of guideline-based care and shared decision-making in the SCI population with neurogenic lower urinary tract dysfunction.


Assuntos
Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Humanos , Bexiga Urinária , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/terapia , Preferência do Paciente , Tomada de Decisão Clínica , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia
8.
Sci Rep ; 14(1): 7691, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565845

RESUMO

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.


Assuntos
Traumatismos da Medula Espinal , Tuberculose da Coluna Vertebral , Humanos , Estudos Prospectivos , Tuberculose da Coluna Vertebral/complicações , Traumatismos da Medula Espinal/complicações , Algoritmos , Aprendizado de Máquina , Estudos Retrospectivos
9.
Ann Med ; 56(1): 2333890, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38557236

RESUMO

Medical security support for rehabilitation therapy in China is different from that in other countries. We investigated whether the discharge plan to continue rehabilitation therapy in tertiary hospitals for patients after traumatic spinal cord injury (TSCI) was influenced by payment sources or other conditions. This was a cross-sectional, observational study. Information was collected on the general condition, caregiver, types of payment sources for continued rehabilitation, American Spinal Injury Association Impairment Scale (AIS) scores, and discharge plans. In total, 135 patients with TSCI (107 male, mean age 41.00 ± 13.73 years, mean spinal cord injury duration 238.43 ± 345.54 days) were enrolled. Medical insurance (43%) and out-of-pocket payments (27.4%) were the primary payment sources. Although most patients were beyond the acute phase, 40% continued rehabilitation therapy at other tertiary hospitals. The caregiver, payment sources, injury level, AIS level, and complete urinary tract infection (UTI) were different due to discharge plans (p > .05). Patients seemingly consider a higher AIS level and co-UTI as the requirement for tertiary hospital therapy. In non-medical insurance payment source patients, the discharge plan also differed due to the AIS level and co-UTI (p > .05). However, in medical insurance patients, the discharge plan differed only in terms of TSCI duration (p > .05). The restricted duration of medical coverage restricted the continuation of rehabilitation therapy and influenced the discharge plan of most patients with TSCI.


Assuntos
Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Infecções Urinárias , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Centros de Atenção Terciária , Alta do Paciente , Estudos Transversais , Traumatismos da Medula Espinal/reabilitação , Estudos Retrospectivos
10.
Nat Commun ; 15(1): 2201, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561341

RESUMO

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Transplante Autólogo/efeitos adversos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/complicações , Traumatismos da Coluna Vertebral/complicações , Resultado do Tratamento
11.
Spinal Cord Ser Cases ; 10(1): 20, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600074

RESUMO

STUDY DESIGN: Feasibility study. OBJECTIVE: To determine the feasibility of conducting a large trial designed to determine whether the ROBERT® can be used to increase the strength of the hip flexor muscles after spinal cord injury (SCI). The ROBERT® is a robotic device that provides assisted active movement while supporting the weight of the leg. Focus was on recruitment capability, suitability, and acceptability of the intervention and outcome measure. SETTING: Specialised SCI centre in Denmark. METHODS: All first-time admitted patients were screened to assess participant recruitment capability. Four people with SCI < 3 months tested a protocol consisting of 60 repetitions of hip flexion in supine conducted with the assistance of the ROBERT® three times a week for 4 weeks. Feasibility was assessed based on adherence to the protocol and completion rate and from the participants' perspectives. Maximal voluntary contraction (MVC) was accessed at baseline and four weeks. RESULTS: The recruitment rate was 8% (7 months). The four participants completed 44 out of 48 sessions (92%). No adverse events occurred. One physiotherapist was required to set-up and supervise each session. The active exercise time varied from 7.5 to 17 min. The participants found the ROBERT® a good supplement to their usual rehabilitation. We were able to measure MVC in even very weak hip flexor muscles with a dynamometer MicroFET2 fixed to a frame. CONCLUSION: The ROBERT® was feasible and acceptable. The participants perceived it as a supplement, not a replacement to usual physiotherapy. However, recruitment to the study was slow. TRIAL REGISTRATION: ClinicalTrials.gov NCT05558254. Registered 28th September 2022.


Assuntos
Procedimentos Cirúrgicos Robóticos , Traumatismos da Medula Espinal , Humanos , Estudos de Viabilidade , Traumatismos da Medula Espinal/reabilitação , Força Muscular , Músculos
12.
J Orthop Surg Res ; 19(1): 230, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589918

RESUMO

BACKGROUND: Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Previous studies have revealed the critical influence of trans-acting transcription factor 1 (SP1) in neurological pathologies, however, its role and mechanism in SCI have not been fully studied. METHODS: The study was performed using mouse microglia BV2 stimulated using lipopolysaccharide (LPS) and male adult mice subjected to spinal hitting. Western blotting was performed to detect protein expression of SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x protein (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters of differentiation 86 (CD86), Arginase 1 (Arg-1) and clusters of differentiation 206 (CD206). Cell viability and apoptosis were analyzed by MTT assay and TUNEL assay. mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-4 (IL-4) and tumor necrosis factor-ß (TNF-ß) were quantified by quantitative real-time polymerase chain reaction. The association of SP1 and HTR2B was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. HE staining assay was performed to analyze the pathological conditions of spinal cord tissues. RESULTS: LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing. Mechanism assays revealed that SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization. Moreover, SP1 absence inhibited BV2 cell apoptosis and promoted microglia polarization from M1 to M2 phenotype by decreasing HTR2B expression. SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization. CONCLUSION: SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization.


Assuntos
Microglia , Traumatismos da Medula Espinal , Camundongos , Masculino , Animais , Microglia/metabolismo , Lipopolissacarídeos/farmacologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
13.
J Neuroeng Rehabil ; 21(1): 50, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594696

RESUMO

BACKGROUND: The pendulum test is a quantitative method used to assess knee extensor spasticity in humans with spinal cord injury (SCI). Yet, the clinical implementation of this method remains limited. The goal of our study was to develop an objective and portable system to assess knee extensor spasticity during the pendulum test using inertial measurement units (IMU). METHODS: Spasticity was quantified by measuring the first swing angle (FSA) using a 3-dimensional optical tracking system (with external markers over the iliotibial band, lateral knee epicondyle, and lateral malleolus) and two wireless IMUs (positioned over the iliotibial band and mid-part of the lower leg) as well as a clinical exam (Modified Ashworth Scale, MAS). RESULTS: Measurements were taken on separate days to assess test-retest reliability and device agreement in humans with and without SCI. We found no differences between FSA values obtained with the optical tracking system and the IMU-based system in control subjects and individuals with SCI. FSA values from the IMU-based system showed excellent agreement with the optical tracking system in individuals with SCI (ICC > 0.98) and good agreement in controls (ICC > 0.82), excellent test-retest reliability across days in SCI (ICC = 0.93) and good in controls (ICC = 0.87). Notably, FSA values measured by both systems showed a strong association with MAS scores ( ρ  ~ -0.8) being decreased in individuals with SCI with higher MAS scores, reflecting the presence of spasticity. CONCLUSIONS: These findings suggest that our new portable IMU-based system provides a robust and flexible alternative to a camera-based optical tracking system to quantify knee extensor spasticity following SCI.


Assuntos
Extremidade Inferior , Traumatismos da Medula Espinal , Humanos , Reprodutibilidade dos Testes , Espasticidade Muscular/etiologia , Espasticidade Muscular/complicações , Joelho , Traumatismos da Medula Espinal/complicações
14.
PLoS One ; 19(4): e0300318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564576

RESUMO

This study aimed to develop and evaluate the ARM (arm repetitive movement) algorithm using inertial measurement unit (IMU) data to assess repetitive arm motion in manual wheelchair (MWC) users in real-world settings. The algorithm was tested on community data from four MWC users with spinal cord injury and compared with video-based analysis. Additionally, the algorithm was applied to in-home and free-living environment data from two and sixteen MWC users, respectively, to assess its utility in quantifying differences across activities of daily living and between dominant and non-dominant arms. The ARM algorithm accurately estimated active and resting times (>98%) in the community and confirmed asymmetries between dominant and non-dominant arm usage in in-home and free-living environment data. Analysis of free-living environment data revealed that the total resting bout time was significantly longer (P = 0.049) and total active bout time was significantly shorter (P = 0.011) for the non-dominant arm. Analysis of active bouts longer than 10 seconds showed higher total time (P = 0.015), average duration (P = 0.026), and number of movement cycles per bout (P = 0.020) for the dominant side. These findings support the feasibility of using the IMU-based ARM algorithm to assess repetitive arm motion and monitor shoulder disorder risk factors in MWC users during daily activities.


Assuntos
Doenças Musculoesqueléticas , Traumatismos da Medula Espinal , Cadeiras de Rodas , Humanos , Atividades Cotidianas , Traumatismos da Medula Espinal/etiologia , Cadeiras de Rodas/efeitos adversos , Algoritmos , Doenças Musculoesqueléticas/etiologia , Fatores de Risco
15.
Spinal Cord Ser Cases ; 10(1): 16, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570486

RESUMO

INTRODUCTION: NeuroAiD (MLC601 & MLC901)'s neuroprotective capabilities include limiting exaggerated calcium influx, decreasing excitotoxicity, reducing oxidative stress, and preventing glutamate-induced cell death. It has also been shown to facilitate synaptogenesis, neurogenesis, and neuroplasticity. However, its clinical efficacy has primarily been studied in the context of brain injuries, particularly stroke. NeuroAiD's potential application in SCI remains largely untapped. CASE PRESENTATION: A 34-year-old male presented with C4 complete tetraplegia. Following surgical decompression and initial inpatient rehabilitation, he started consuming MLC901 two capsules three times daily at month 4 post injury for 6 months. He regained considerable neurological recovery following the supplementation. Apart from the improvement in the neurological level of injury, the patient exhibited motor recovery beyond the initial zone of partial preservation up to 24 months post injury. DISCUSSION: Our findings align with a recent animal study demonstrating MLC901's potential to downregulate Vascular Endothelial Growth Factor (VEGF), a molecule known to increase vascular permeability and exacerbate tissue edema and infarction. In another animal study involving stroke-affected mice, MLC901 demonstrates the ability to promote neurological recovery by regulating the expression of proteins mediating angiogenesis, such as hypoxic inducible factor 1α, erythropoietin, angiopoietins 1 and 2, as well as VEGF. The anecdotal findings from this case report offer preliminary insights into NeuroAiD's potential in facilitating recovery during post-acute and chronic phases of severe SCI, necessitating further exploration.


Assuntos
Medicamentos de Ervas Chinesas , Traumatismos da Medula Espinal , Acidente Vascular Cerebral , Masculino , Humanos , Animais , Camundongos , Adulto , Fator A de Crescimento do Endotélio Vascular/metabolismo , Traumatismos da Medula Espinal/complicações , Medicamentos de Ervas Chinesas/farmacologia
16.
BMC Pediatr ; 24(1): 236, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570804

RESUMO

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.


Assuntos
Traumatismos da Medula Espinal , Masculino , Feminino , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia , Radiografia , Prognóstico , China/epidemiologia , Imageamento por Ressonância Magnética
17.
Cell Transplant ; 33: 9636897241241998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590295

RESUMO

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.


Assuntos
Traumatismos da Medula Espinal , Transplante de Células-Tronco , Humanos , Neurônios , Medula Espinal
18.
Sci Rep ; 14(1): 8290, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594283

RESUMO

Traumatic spinal cord injury (TSCI) has significant physical, psychological, and socioeconomic impacts. However, the epidemiological characteristics and treatment patterns of TSCI in South Korea remain unclear. This study aimed to investigate TSCI incidence and treatment behaviors in South Korea from 2008 to 2020. We included data from 30,979 newly diagnosed TSCI patients obtained from the Health Insurance Review and Assessment Service (HIRA). Treatment trends, location of surgery, surgical method, comorbidities, factors affecting hospital stay, and risk factors affecting readmission were analyzed. Patients were divided into the surgery group [n = 7719; (25%)] and the non-surgery group [n = 23,260; (75%)]. Surgical cases involved cervical (64%), thoracic (17%), and lumbar/sacral (19%) lesions. Anterior fusion (38%), posterior fusion (54%), and corpectomy (8%) were the surgical methods. Surgical treatments increased annually. Factors influencing hospital stay included male sex, older age, and higher Charlson comorbidity index (CCI). Female sex and higher CCI scores were associated with readmission. In conclusion, a quarter of all TSCI patients underwent surgery, with an upward trend. Risk factors for longer hospital stays were thoracic spine injury, older age, higher CCI, and male sex. Risk factors for readmission included age range of 40-59 years, lumbar/sacral spine injuries, CCI score of 2, and female sex.


Assuntos
Lesões nas Costas , Traumatismos da Medula Espinal , Doenças da Coluna Vertebral , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/cirurgia , Comorbidade , Tempo de Internação , Doenças da Coluna Vertebral/complicações , Estudos Retrospectivos
19.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 68(2): 151-158, Mar-Abr. 2024. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-231897

RESUMO

Introducción: La lesión medular tipo SCIWORA es una entidad clínica con baja incidencia y alta repercusión funcional. El objetivo del estudio es la descripción epidemiológica de esta lesión y su evolución funcional con un seguimiento medio de 10 años. Material y métodos: Estudio analítico, longitudinal, de cohortes ambispectivo. Fueron evaluados 13 pacientes con el diagnóstico de SCIWORA en el periodo de estudio 2001-2022. Variables evaluadas: edad, sexo, días hasta la lesión medular, causa de lesión, imagen medular en la RM postraumatismo, nivel neurológico de lesión, ASIA ingreso/alta/5 años, SCIM III ingreso/alta/3 años, tipo de tratamiento empleado, empleo de terapia NASCIS III ingreso, tiempo de hospitalización, seguimiento medio. En octubre del 2022 fueron nuevamente evaluados en consultas externas mediante: cuestionario de discapacidad cervical (NDI)/Oswestry y cuestionario de calidad de vida validado en castellano para lesionados medulares (SV-QLI/SCI). Resultados: La mediana de edad fue de 4 años, 77% varones. El 54% de las lesiones corresponden a nivel cervical. El ASIA al ingreso fue del 31% A y del 31% C, nivel neurológico: C2 (22%) y T10 (15%), tráfico como causa de lesión (77%), SCIM III ingreso/alta: 28,5/42. La estancia media hospitalaria fue de 115 días. NDI: 11,6 y Oswestry: 15,3. Conclusión: El 77% de los SCIWORA se producen en menores de 8 años. Al año del alta hospitalaria un 31% de los pacientes fueron catalogados como ASIA D y a los 5 años el porcentaje se mantiene constante. No se encontraron diferencias significativas entre la causa de la lesión y tipo de alteración en RM (p = 0,872), ni entre la edad y el tipo de lesión medular objetivada en RM (p = 0,149).(AU)


Introduction: SCIWORA has a low incidence but a high functional repercussion. The aim of the present study was to characterize the epidemiology of this clinical-radiological condition and evaluate functional outcome with a mean of 10-years follow-up. Material and methods: Observational, longitudinal ambispective cohort study. Thirteen SCIWORA patients were admitted in the study period. Demographics, mechanism of injury, spinal cord MRI findings, neurological level of injury, time to SCI, neurological status (AIS) at admission/discharge/5 years, spinal cord independence measure (SCIM III) scale at admission and discharge, hospital length of stay and mean follow-up were recorded. On October 2022 patients were re-evaluated using NDI, Oswestry, and SV-QLI/SCI. Results: Median age was 4 years. The study population for this investigation was mostly men (77%). 54% of level of injury correspond to cervical spine. AIS at admission was A (31%) and C (31%). Neurological level of injury was C2 (22%) and T10 (15%). Motor vehicle-related injury was the most prevalent mechanism of injury (77%), SCIM III scale at admission and discharge: 28.5/42, hospital length of stay was 115 days. The NDI was 11.6, Oswestry: 15.3 and SV-QLI/SCI: 17. Conclusions: Seventy-seven percent of SCIWORA patients was detected under 8 years-old. At 1 year follow-up after discharge 31% patients were AIS grade D and with 5 years follow-up the percentage remain constant. No statistically significant differences in the mechanism of injury and MRI findings (P = 0.872), age and MRI spinal cord findings (P = 0.149) were found in SCIWORA patients.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Traumatologia , Estudos Longitudinais , Estudos de Coortes , Pediatria
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(4): 480-486, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38632070

RESUMO

Objective: To explore the therapeutic effect of basic fibroblast growth factor (bFGF) on spinal cord injury (SCI) in rats and the influence of Notch/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods: A total of 40 10-week-old male Sprague Dawley (SD) rats were selected to establish T 10-segment SCI model by a free falling object. Among them, 32 successful models were randomly divided into model group and bFGF group, with 16 in each group. Another 16 SD rats were selected as sham-operation group, with only T 10 processes, dura mater, and spinal cord exposed. After modeling, the rats in bFGF group were intraperitoneally injected with 100 µg/kg bFGF (once a day for 28 days), and the rats in model group and sham-operation group were injected with normal saline in the same way. The survival of rats in each group were observed after modeling. Basso-Beattie-Bresnahan (BBB) scores were performed before modeling and at immediate, 14 days, and 28 days after modeling to evaluate the functional recovery of hind limbs. Then, the spinal cord tissue at the site of injury was taken at 28 days and stained with HE, Nissl, and propidium iodide (PI) to observe the pathological changes, neuronal survival (number of Nissl bodies) and apoptosis (number of PI red stained cells) of the spinal cord tissue; immunohistochemical staining and ELISA were used to detect the levels of astrocyte activation markers [glial fibrillary acidic protein (GFAP)] and inflammatory factors [interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ)] in tissues, respectively. Western blot was used to detect the expressions of Notch/STAT3 signaling pathway related proteins [Notch, STAT3, phosphoryl-STAT3 (p-STAT3), bone morphogenetic protein 2 (BMP-2)] in tissues. Results: All rats survived until the experiment was completed. At immediate after modeling, the BBB scores in model group and bFGF group significantly decreased when compared to sham-operation group ( P<0.05). At 14 and 28 days after modeling, the BBB scores in model group significantly decreased when compared to sham-operation group ( P<0.05); the bFGF group showed an increase compared to model group ( P<0.05). Compared with before modeling, the BBB scores of model group and bFGF group decreased at immediate after modeling, and gradually increased at 14 and 28 days, the differences between different time points were significant ( P<0.05). The structure of spinal cord tissue in sham-operation group was normal; in model group, there were more necrotic lesions in the spinal cord tissue and fewer Nissl bodies with normal structures; the number of necrotic lesions in the spinal cord tissue of the bFGF group significantly reduced compared to the model group, and some normally structured Nissl bodies were visible. Compared with sham-operation group, the number of Nissl bodies in spinal cord tissue significantly decreased, the number of PI red stained cells, GFAP, IL-1ß, TNF-α, IFN-γ, Notch, p-STAT3 /STAT3, BMP-2 protein expression levels significantly increased in model group ( P<0.05). The above indexes in bFGF group significantly improved when compared with model group ( P<0.05). Conclusion: bFGF can improve motor function and pathological injury repair of spinal cord tissue in SCI rats, improve neuronal survival, and inhibit neuronal apoptosis, excessive activation of astrocytes in spinal cord tissue and inflammatory response, the mechanism of which may be related to the decreased activity of Notch/STAT3 signaling pathway.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Traumatismos da Medula Espinal , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Fator de Transcrição STAT3/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Traumatismos da Medula Espinal/terapia , Medula Espinal/metabolismo , Transdução de Sinais
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