Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.104
Filtrar
1.
Front Pharmacol ; 15: 1419797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994202

RESUMO

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

2.
Stem Cell Res Ther ; 15(1): 204, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978125

RESUMO

Spinal cord injury (SCI) is a complex tissue injury that results in a wide range of physical deficits, including permanent or progressive disabilities of sensory, motor and autonomic functions. To date, limitations in current clinical treatment options can leave SCI patients with lifelong disabilities. There is an urgent need to develop new therapies for reconstructing the damaged spinal cord neuron-glia network and restoring connectivity with the supraspinal pathways. Neural stem cells (NSCs) possess the ability to self-renew and differentiate into neurons and neuroglia, including oligodendrocytes, which are cells responsible for the formation and maintenance of the myelin sheath and the regeneration of demyelinated axons. For these properties, NSCs are considered to be a promising cell source for rebuilding damaged neural circuits and promoting myelin regeneration. Over the past decade, transplantation of NSCs has been extensively tested in a variety of preclinical models of SCI. This review aims to highlight the pathophysiology of SCI and promote the understanding of the role of NSCs in SCI repair therapy and the current advances in pathological mechanism, pre-clinical studies, as well as clinical trials of SCI via NSC transplantation therapeutic strategy. Understanding and mastering these frontier updates will pave the way for establishing novel therapeutic strategies to improve the quality of recovery from SCI.


Assuntos
Bainha de Mielina , Células-Tronco Neurais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Humanos , Células-Tronco Neurais/transplante , Células-Tronco Neurais/citologia , Bainha de Mielina/metabolismo , Animais , Regeneração Nervosa/fisiologia , Transplante de Células-Tronco/métodos
3.
Artif Organs ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884389

RESUMO

BACKGROUND: Functional electrical stimulation (FES) cycling has been reported to enhance muscle strength and improve muscle fatigue resistance after spinal cord injury (SCI). Despite its proposed benefits, the quantification of muscle fatigue during FES cycling remains poorly documented. This study sought to quantify the relationship between the vibrational performance of electrically-evoked muscles measured through mechanomyography (MMG) and its oxidative metabolism through near-infrared spectroscopy (NIRS) characteristics during FES cycling in fatiguing paralyzed muscles in individuals with SCI. METHODS: Six individuals with SCI participated in the study. They performed 30 min of FES cycling with MMG and NIRS sensors on their quadriceps throughout the cycling, and the signals were analyzed. RESULTS: A moderate negative correlation was found between MMG root mean square (RMS) and oxyhaemoglobin (O2Hb) [r = -0.38, p = 0.003], and between MMG RMS and total hemoglobin (tHb) saturation [r = -0.31, p = 0.017]. Statistically significant differences in MMG RMS, O2Hb, and tHb saturation occurred during pre- and post-fatigue of FES cycling (p < 0.05). CONCLUSIONS: MMG RMS was negatively associated with O2Hb and muscle oxygen derived from NIRS. MMG and NIRS sensors showed good inter-correlations, suggesting a promising use of MMG for characterizing metabolic fatigue at the muscle oxygenation level during FES cycling in individuals with SCI.

4.
JMIR Res Protoc ; 13: e56081, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865699

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a devastating condition that often leads to significant impairments in physical function, leading to disability and mental health disorders. Hence, understanding the prevalence of SCI and the relationship between physical activity and mental health in individuals with SCI is crucial for informing rehabilitation strategies and optimizing outcomes. OBJECTIVE: This study aims to comprehensively analyze existing research on the link between physical activity and mental health and identify the level of physical activity and mental health status, the barriers to physical activity, and SCI's impacts on psychological well-being in individuals with SCI. METHODS: An electronic search strategy will be used to identify prevalence studies published since 1993 in health-related databases such as PubMed, MEDLINE, COCHRANE Library, and Wiley Library using the following query: "Spinal Cord Injury" OR "Paraplegia" OR "Tetraplegia" AND "Physical Activity" OR "Exercise" AND "Mental Health" OR "Mental Illness" OR "Mental Disorder." Bibliographies of primary studies and review articles meeting the inclusion criteria will be searched manually to identify further eligible studies. The risk of bias in the included studies will be appraised using the Joanna Briggs Institute checklist for prevalence studies by 2 review authors. Any disagreement will be resolved by reaching a consensus. RESULTS: Funding was received in October 2023, data collection will commence in July 2024, and the results are expected by 2025. We will summarize the selection of the eligible studies using a flowchart. The data from the studies will be extracted and tabulated. This scoping review will be published in a peer-reviewed journal in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. CONCLUSIONS: This scoping review underscores the complex relationship between physical activity and mental health among individuals with SCI, highlighting the level of physical activity and mental health status, barriers to physical activity engagement, and psychological implications. Understanding these dynamics is crucial in devising tailored interventions aimed at enhancing mental well-being. This synthesis of evidence emphasizes the need for personalized strategies to promote physical activity, addressing unique challenges faced by this population to foster improved mental health outcomes and overall quality of life. TRIAL REGISTRATION: Open Science Framework osf.io/ugx7d; https://osf.io/ugx7d/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56081.


Assuntos
Exercício Físico , Saúde Mental , Traumatismos da Medula Espinal , Humanos , Exercício Físico/psicologia , Traumatismos da Medula Espinal/psicologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/epidemiologia , Revisões Sistemáticas como Assunto
5.
Biomed Pharmacother ; 176: 116938, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878684

RESUMO

Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory and motor dysfunction. It has been reported that signaling pathway plays a key role in the pathological process and neuronal recovery mechanism of SCI. Such as PI3K/Akt, MAPK, NF-κB, and Wnt/ß-catenin signaling pathways. According to reports, various stimuli and cytokines activate these signaling pathways related to SCI pathology, thereby participating in the regulation of pathological processes such as inflammation response, cell apoptosis, oxidative stress, and glial scar formation after injury. Activation or inhibition of relevant pathways can delay inflammatory response, reduce neuronal apoptosis, prevent glial scar formation, improve the microenvironment after SCI, and promote neural function recovery. Based on the role of signaling pathways in SCI, they may be potential targets for the treatment of SCI. Therefore, understanding the signaling pathway and its inhibitors may be beneficial to the development of SCI therapeutic targets and new drugs. This paper mainly summarizes the pathophysiological process of SCI, the signaling pathways involved in SCI pathogenesis, and the potential role of specific inhibitors/activators in its treatment. In addition, this review also discusses the deficiencies and defects of signaling pathways in SCI research. It is hoped that this study can provide reference for future research on signaling pathways in the pathogenesis of SCI and provide theoretical basis for SCI biotherapy.


Assuntos
Transdução de Sinais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Animais
6.
Biomed Eng Online ; 23(1): 58, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902756

RESUMO

BACKGROUND: Heart rate variability (HRV) may provide objective information about cardiogenic autonomic balance in individuals with spinal cord injury (SCI). The aim of this study was to characterize the diurnal variation of HRV in individuals with SCI at lesion level T6 and above and lesion level below T6. METHODS: This was a retrospective analysis of a prior cross-sectional study. Individuals with chronic SCI underwent 24 h recording of the time between consecutive R waves (RR interval) to derive parameters of HRV as follows: standard deviation of all normal-to-normal R-R intervals (SDNN) and square root of the mean of the squared differences between successive R-R intervals (RMSSD) (time domain); and high frequency power (HF), low-frequency power (LF), very low frequency power (VLF), ultra-low frequency power (ULF) and total power (TP) (frequency domain). Changes in the magnitude of HRV outcomes over the 24 h period were investigated using a novel multi-component cosinor model constrained to the form of a three-harmonic Fourier series. RESULTS: Participants were grouped as lesion level T6 and above (n = 22) or below T6 (n = 36). Most of them were male (n = 40, 69%) and the median age (interquartile range) was 50.5 (28) years. Both groups exhibited similar diurnal patterns in most HRV metrics. The lowest values occurred in the late afternoon (4-6 pm) and gradually increased, peaking around midnight to early morning (1-6 am). Exceptions included RMSSD, which peaked before midnight, and ULF, which showed a double peak pattern that peaked from 11 am to 1 pm and 4-6 am in participants with lesion level at T6 and above. The HRV values in participants with lesion level T6 and above were generally lower than participants with lesion level below T6, except for peak values of RMSSD, HF and LF. CONCLUSION: This study demonstrated substantial diurnal variation of HRV in participants with SCI in both groups of participants. In clinical and research settings, diurnal variations in HRV must be taken into consideration.


Assuntos
Ritmo Circadiano , Frequência Cardíaca , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Estudos Transversais , Estudos Retrospectivos
7.
Sci Rep ; 14(1): 14023, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890348

RESUMO

The mechanism of spinal cord injury (SCI) is highly complex, and an increasing number of studies have indicated the involvement of pyroptosis in the physiological and pathological processes of secondary SCI. However, there is limited bioinformatics research on pyroptosis-related genes (PRGs) in SCI. This study aims to identify and validate differentially expressed PRGs in the GEO database, perform bioinformatics analysis, and construct regulatory networks to explore potential regulatory mechanisms and therapeutic targets for SCI. We obtained high-throughput sequencing datasets of SCI in rats and mice from the GEO database. Differential analysis was conducted using the "limma" package in R to identify differentially expressed genes (DEGs). These genes were then intersected with previously reported PRGs, resulting in a set of PRGs in SCI. GO and KEGG enrichment analyses, as well as correlation analysis, were performed on the PRGs in both rat and mouse models of SCI. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING website to examine the relationships between proteins. Hub genes were identified using Cytoscape software, and the intersection of the top 5 hub genes in rats and mice were selected for subsequent experimentally validated. Furthermore, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory mechanisms. The gene expression profiles of GSE93249, GSE133093, GSE138637, GSE174549, GSE45376, GSE171441_3d and GSE171441_35d were selected in this study. We identified 10 and 12 PRGs in rats and mice datasets respectively. Six common DEGs were identified in the intersection of rats and mice PRGs. Enrichment analysis of these DEGs indicated that GO analysis was mainly focused on inflammation-related factors, while KEGG analysis showed that the most genes were enriched on the NOD-like receptor signaling pathway. We constructed a ceRNA regulatory network that consisted of five important PRGs, as well as 24 miRNAs and 34 lncRNAs. This network revealed potential regulatory mechanisms. Additionally, the three hub genes obtained from the intersection were validated in the rat model, showing high expression of PRGs in SCI. Pyroptosis is involved in secondary SCI and may play a significant role in its pathogenesis. The regulatory mechanisms associated with pyroptosis deserve further in-depth research.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Piroptose , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Camundongos , Piroptose/genética , Ratos , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Perfilação da Expressão Gênica
8.
NeuroRehabilitation ; 54(4): 611-618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875052

RESUMO

BACKGROUND: Urinary dysfunction is linked to spinal cord injury (SCI). The quality of life (QoL) declines in both neurogenic bladder impairment and non-disordered patients. OBJECTIVE: To ascertain the effectiveness of pulsed magnetic therapy on urinary impairment and QoL in individuals with traumatic incomplete SCI. METHODS: This study included forty male paraplegic subjects with neurogenic detrusor overactivity (NDO) for more than one year following incomplete SCI between T6-T12. Their ages ranged from 20 to 35 and they engaged in therapy for three months. The subjects were divided into two groups of equal size. Individuals in Group I were managed via pulsed magnetic therapy once per week plus pelvic floor training three times a week. Individuals in Group II were managed with only three times a week for pelvic floor training. All patients were examined for bladder cystometric investigations, pelvic-floor electromyography (EMG), and SF-Qualiveen questionnaire. RESULTS: There was a noteworthy increment in individuals in Group I in volume of bladder at first desire to void and maximum cystometric capacity, detrusor pressure at Qmax, and maximum flow rate. There was a momentous increment in Group I in measures of evaluation of EMG biofeedback. There was a notable rise in Group I in SF-Qualiveen questionnaire. CONCLUSION: Magnetic stimulation should be favored as beneficial adjunct to traditional therapy in the management of bladder impairment and enhancing QoL in individuals with SCI.


Assuntos
Magnetoterapia , Paraplegia , Qualidade de Vida , Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Humanos , Masculino , Adulto , Magnetoterapia/métodos , Paraplegia/reabilitação , Paraplegia/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/fisiopatologia , Adulto Jovem , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/reabilitação , Diafragma da Pelve/fisiopatologia , Resultado do Tratamento , Eletromiografia , Inquéritos e Questionários , Urodinâmica/fisiologia
9.
BMC Urol ; 24(1): 122, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867233

RESUMO

BACKGROUND: Neurogenic bladder dysfunction is a major problem for spinal cord injury (SCI) patients not only due to the risk of serious complications but also because of the impact on quality of life. The main aim of this study is to compare the rate of urinary tract infection (UTI) associated with hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters among SCI patients presenting with functional neurogenic bladder sphincter disorders. METHODOLOGY: This was a retrospective cohort study from 2005 to 2020 including adult male or female patients who have an SCI at least more than 1 month ago with neurogenic bladder dysfunction and were using intermittent catheterization (single-use hydrophilic-coated or the standard-of-care polyvinyl chloride uncoated standard catheters) at least 3 times a day to maintain bladder emptying. RESULTS: A total of 1000 patients were selected and recruited through a stratified random sampling technique with 467 (47.60%) patients in the uncoated catheter arm and 524 (52.60%) in the coated catheter groups. The three outcome measures, namely: symptomatic UTI, Bacteriuria, and pyuria were significantly higher in the group using uncoated polyvinyl chloride (PVC) catheters compared to hydrophilic-coated catheters at the rate of 79.60% vs.46.60%, 81.10% vs. 64.69, and 53.57% versus 41.79% respectively. Males, elder patients, longer duration, and severity of SCI were associated with increased risk of symptomatic UTI. CONCLUSIONS: The results indicate a beneficial effect regarding clinical UTI when using hydrophilic-coated catheters in terms of fewer cases of symptomatic UTI. Bacteriuria is inevitable in patients with long-term catheterization, however, treatment should not be started unless the clinical symptoms exist. More attention should be given to the high-risk group for symptomatic UTIs.


Assuntos
Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Infecções Urinárias , Humanos , Estudos Retrospectivos , Traumatismos da Medula Espinal/complicações , Masculino , Feminino , Infecções Urinárias/etiologia , Infecções Urinárias/epidemiologia , Pessoa de Meia-Idade , Adulto , Cateteres Urinários/efeitos adversos , Cateterismo Uretral Intermitente/efeitos adversos , Interações Hidrofóbicas e Hidrofílicas , Cloreto de Polivinila , Estudos de Coortes , Idoso , Cateterismo Urinário/efeitos adversos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia
10.
Int Urol Nephrol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935323

RESUMO

PURPOSE: To investigate the effects of low-intensity extracorporeal shock wave therapy (LiESWT) on bladder and urethral dysfunction with detrusor overactivity and detrusor sphincter dyssynergia (DSD) resulting from spinal cord injury (SCI). METHODS: At 3 weeks after Th9 spinal cord transection, LiESWT was performed on the bladder and urethra of adult female Sprague Dawley rats with 300 shots of 2 Hz and an energy flux density of 0.12 mJ/mm2, repeated four times every 3 days, totaling 1200 shots. Six weeks postoperatively, a single cystometrogram (CMG) and an external urethral sphincter electromyogram (EUS-EMG) were simultaneously recorded in awake animals, followed by histological evaluation. RESULTS: Voiding efficiency significantly improved in the LiESWT group (71.2%) compared to that in the control group (51.8%). The reduced EUS activity ratio during voiding (duration of reduced EUS activity during voiding/EUS contraction duration with voiding + duration of reduced EUS activity during voiding) was significantly higher in the LiESWT group (66.9%) compared to the control group (46.3%). Immunohistochemical examination revealed that fibrosis in the urethral muscle layer was reduced, and S-100 stained-positive area, a Schwann cell marker, was significantly increased in the urethra of the LiESWT group. CONCLUSION: LiESWT targeting the urethra after SCI can restore the EUS-EMG tonic activity during voiding, thereby partially ameliorating DSD. Therefore, LiESWT is a promising approach for treating bladder and urethral dysfunction following SCI.

11.
Arch Bone Jt Surg ; 12(6): 380-399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919744

RESUMO

Spinal cord injury (SCI) is a complex, multifaceted, progressive, and yet incurable complication that can cause irreversible damage to the individual, family, and society. In recent years strategies for the management and rehabilitation of SCI besides axonal regeneration, remyelination, and neuronal plasticity of the injured spinal cord have significantly improved. Although most of the current research and therapeutic advances have been made in animal models, so far, no specific and complete treatment has been reported for SCI in humans. The failure to treat this complication has been due to the inherent neurological complexity and the structural, cellular, molecular, and biochemical characteristics of spinal cord injury. In this review, in addition to elucidating the causes of spinal cord injury from a molecular and pathophysiological perspective, the complexity and drawbacks of neural regeneration that lead to the failure in SCI treatment are described. Also, recent advances and cutting-edge strategies in most areas of SCI treatment are presented.

12.
Exp Neurol ; 378: 114816, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38789023

RESUMO

High spinal cord injury (SCI) leads to persistent and debilitating compromise in respiratory function. Cervical SCI not only causes the death of phrenic motor neurons (PhMNs) that innervate the diaphragm, but also damages descending respiratory pathways originating in the rostral ventral respiratory group (rVRG) located in the brainstem, resulting in denervation and consequent silencing of spared PhMNs located caudal to injury. It is imperative to determine whether interventions targeting rVRG axon growth and respiratory neural circuit reconnection are efficacious in chronic cervical contusion SCI, given that the vast majority of individuals are chronically-injured and most cases of SCI involve contusion-type damage to the cervical region. We therefore employed a rat model of chronic cervical hemicontusion to test therapeutic manipulations aimed at reconstructing damaged rVRG-PhMN-diaphragm circuitry to achieve recovery of respiratory function. At a chronic time point post-injury, we systemically administered: an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential; an antagonist peptide directed against receptor-type protein tyrosine phosphatase sigma (PTPσ), another important negative regulator of axon growth capacity; or a combination of these two peptides. PTEN antagonist peptide (PAP4) promoted partial recovery of diaphragm motor activity out to nine months post-injury (though this effect depended on the anesthetic regimen used during recording), while PTPσ peptide did not impact diaphragm function after cervical SCI. Furthermore, PAP4 promoted robust growth of descending bulbospinal rVRG axons caudal to the injury within the denervated portion of the PhMN pool, while PTPσ peptide did not affect rVRG axon growth at this location that is critical to control of diaphragmatic respiratory function. In conclusion, we find that, when PTEN inhibition is targeted at a chronic time point following cervical contusion, our non-invasive PAP4 strategy can successfully promote significant regrowth of damaged respiratory neural circuitry and also partial recovery of diaphragm motor function.


Assuntos
Axônios , Diafragma , PTEN Fosfo-Hidrolase , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Feminino , Ratos , Axônios/efeitos dos fármacos , Medula Cervical/lesões , Doença Crônica , Diafragma/inervação , Modelos Animais de Doenças , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Ratos Sprague-Dawley , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/antagonistas & inibidores , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Recuperação de Função Fisiológica/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia
13.
Int Immunopharmacol ; 134: 112188, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728880

RESUMO

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/AKT/GSK3ß and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/AKT/GSK3ß signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.


Assuntos
Glicogênio Sintase Quinase 3 beta , Macrófagos , Microglia , NF-kappa B , Regeneração Nervosa , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Regeneração Nervosa/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , NF-kappa B/metabolismo , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Masculino , Axônios/metabolismo , Axônios/efeitos dos fármacos , Axônios/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fenótipo , Ratos , Humanos , Modelos Animais de Doenças , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia
14.
Neurochem Int ; 177: 105759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735393

RESUMO

BACKGROUND: Exosomes generated from adipose-derived mesenchymal stem cells (Exos), and in particular hypoxia-pretreated ADSCs (HExos), possess therapeutic properties that promote spinal cord repair following spinal cord injury (SCI). Nevertheless, the regulatory mechanisms through which HExos exert their effects remain unclear. METHODS: Here, next-generation sequencing (NGS) was utilized to examine abnormal circRNA expression comparing HExos to Exos. Bioinformatics analysis and RNA pulldown assays together with luciferase reporter assays were applied to determine interactions among miRNAs, mRNAs and circRNAs. ELISA and immunofluorescence staining were used to examine inflammatory cytokine levels, apoptosis and ROS deposition in LPS-treated HT-22 cells, respectively. The therapeutic effects of Exos and HExos on a mouse model of SCI were analyzed by immunohistochemistry and immunofluorescence staining. RESULTS: Our findings confirmed that HExos have more significant therapeutic influences on decreasing ROS and inflammatory cytokine levels post-SCI than Exos. NGS revealed that circ-Wdfy3 expression levels were significantly higher in HExos than Exos. Downregulation of circ-Wdfy3 led to a decrease in HExo-induced therapeutic effects on spinal cord repair post-SCI, indicating that circ-Wdfy3 has a critical role in the regulation of HExo-mediated protection against SCI. Our bioinformatics, RNA pulldown and luciferase reporter data demonstrated that GPX4 and miR-423-3p were downstream targets of circ-Wdfy3. GPX4 downregulation or miR-423-3p overexpression reversed the protective effects of circ-Wdfy3 on LPS-treated HT-22 cells. Furthermore, overexpression of circ-Wdfy3 led to an in increase in the Exo-induced therapeutic effects on spinal cord repair post-SCI through the inhibition of ferroptosis. CONCLUSIONS: circ-WDfy3-overexpressing Exos promote spinal cord repair post-SCI through mediation of ferroptosis via the miR-138-5p/GPX4 pathway.


Assuntos
Exossomos , Ferroptose , RNA Circular , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Exossomos/metabolismo , Animais , Ferroptose/fisiologia , RNA Circular/genética , RNA Circular/metabolismo , RNA Circular/biossíntese , Camundongos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo
15.
Top Spinal Cord Inj Rehabil ; 30(2): 65-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799606

RESUMO

Background: Sexual development is a complex process of understanding oneself as a sexual being. Youth with spinal cord injury (SCI) navigate the typical phases of sexual development along with the physical and psychological sequelae of an SCI. As youth with SCI progress from adolescence to emerging adulthood, sexual activity-physical intimacy and sexual intercourse-is an important milestone. Objectives: The aims of the study were to (1) describe frequency of physical intimacy among adults with pediatric-onset SCI and (2) identify injury, demographic, and lifestyle factors that predict frequency of physical intimacy. Methods: Adults with pediatric-onset SCI who were former patients within a North American pediatric hospital system (N = 277) completed a structured telephone interview that included medical and sociodemographic information and standardized measures of psychological functioning. Participants rated physical intimacy and sexual intercourse frequency on a 5-point Likert scale, with a response of monthly, weekly, or daily classified as regular frequency and never or yearly as irregular frequency. Bivariate and multivariate analyses were conducted with physical intimacy frequency as the primary outcome. Results: Of the participants, 55% engaged in physical intimacy and 49% engaged in sexual intercourse with regular frequency. In logistic regression analyses, living independently of parents, being married, and higher perceived social integration increased likelihood of regular frequency of physical intimacy. Injury severity and secondary medical complications were not significant independent predictors of frequency of physical intimacy. Conclusion: Half of adults with pediatric-onset SCI engage in regular physical intimacy; this is below the estimates for the general population. Psychosocial factors are stronger contributors to physical intimacy frequency than SCI-related factors. Health care providers and researchers should focus on barriers to social integration and development of social relationships as factors that influence physical intimacy in this population.


Assuntos
Estilo de Vida , Comportamento Sexual , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/psicologia , Traumatismos da Medula Espinal/complicações , Feminino , Masculino , Adulto , Comportamento Sexual/psicologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Criança , Coito/psicologia
17.
Front Rehabil Sci ; 5: 1395678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818410

RESUMO

Introduction: Spinal cord injury (SCI) affects many aspects of life, physically, emotionally and socially. Engaging in online videogames holds the potential to facilitate increased social interactions for individuals with SCI. The aim of this study is to increase our understanding of the experiences people with SCI have with using online videogames as an arena for social participation. Methods: A focus group interview was conducted with seven participants with SCI, aged 15-35, all experienced in using online videogames as a method of socializing. The data was analyzed using thematic analysis. Results: The participants highlighted that playing online videogames way of maintaining social connections and expanding their social network. However, they faced challenges due to limited knowledge and negative attitudes from others regarding use of videogames as a social arena. Three main themes were developed from the findings: "Disabling social barriers", "Attitudes towards gaming" and "Gaming-connecting people". Conclusion: Healthcare professionals should consider videogames as a leisure activity and facilitate their use, recognizing their potential for social interaction and well-being. Prioritizing activities that promote social interaction is crucial for good health.

18.
J Nepal Health Res Counc ; 21(4): 680-683, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38616602

RESUMO

BACKGROUND: Traumatic cervical spinal injuries can severely affect respiratory function and cause significant morbidity and mortality. The typical respiratory morbidity in cervical spine injury is Atelectasis, Ventilator-associated pneumonia, acute respiratory distress syndrome and delayed weaning, etc. The study aims to see the prevalence of respiratory morbidity as well as mortality associated with cervical spine injury. METHODS: Cross sectional study based on retrospective data was conducted on the X Sciences with the existing hospital record during the period of 3 years to find out the prevalence respiratory morbidity like Ventilatory Associated Pneumonia, delayed weaning, ARDS, atelectasis of traumatic cervical spine injury, determine the prevalence, type, and impact of respiratory morbidity and mortality in this population. RESULTS: Total no 76 patients data meeting the inclusion criteria included in study. Male patients were more prone to develop traumatic cervical spinal injuries (SCI). The prevalence of respiratory morbidity in term of VAP(57.89), delayed weaning(46.05) and Atelectasis(22.36) was high. Patients with Asia A Neurology has higher association for VAP and delayed weaning, while Asia E Neurology patients had no respiratory morbidity. The study found a significant positive association between respiratory morbidity with hospital stay, and ventilator days (p-value: 0.019 and 0.048). A total of 15 patients died, 28.95% were discharged on request and 40.8% leaving the hospital against medical advice. CONCLUSIONS: The prevalence of respiratory morbidity higher in cervical spine injury. Furthermore, it has associated with prolonged ICU and ventilator days and increase in mortality.


Assuntos
Atelectasia Pulmonar , Traumatismos da Coluna Vertebral , Humanos , Masculino , Estudos Transversais , Estudos Retrospectivos , Nepal/epidemiologia , Traumatismos da Coluna Vertebral/epidemiologia
19.
J Vasc Surg ; 80(1): 11-19, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38614137

RESUMO

BACKGROUND: Endovascular techniques have transformed the management of thoracoabdominal aortic aneurysms (TAAAs). However, spinal cord ischemia (SCI) remains a prevalent and devastating complication. Prophylactic drainage of cerebrospinal fluid (CSF) is among the proposed strategies for prevention of SCI. Although prophylactic CSF drainage is widely used and conceptually attractive, prophylactic CSF drains have not been demonstrated to definitively prevent the occurrence nor mitigate the severity of SCI in endovascular TAAA repair. Whether or not outcomes of prophylactic drains are superior to therapeutic drains remains unknown. This pilot study was performed to determine the feasibility of a randomized clinical trial designed to investigate the role of prophylactic vs therapeutic CSF drains in the prevention of SCI in patients undergoing endovascular TAAA repair using branched and fenestrated endovascular aortic repair (FBEVAR). METHODS: This was a prospective multicenter randomized pilot clinical trial conducted at The University of Alabama at Birmingham and The University of Massachusetts. Twenty patients were enrolled and randomized to either the prophylactic drainage or therapeutic drainage groups, prior to undergoing FBEVAR for extensive TAAAs and arch aortic aneurysms. This was a pilot feasibility study that was not powered to detect statistical differences in clinical outcomes. The primary outcome was feasibility of randomization and compliance with a shared lumbar drain protocol. Secondary outcomes included rate of drain complications and SCI. RESULTS: Twenty patients were enrolled and successfully randomized, without any crossovers, to either the control cohort (n = 10), without prophylactic drains, or the experimental cohort (n = 10), with prophylactic drains. There were no differences in age, comorbidities, or history of prior aortic surgery across the cohorts. All patients were treated with FBEVAR. Aneurysm classifications were as follows: Extent I (10%), Extent II (50%), Extent III (35%), and Extent IV (5%). The average length of aortic coverage was 207 ± 21.6 mm. The length of aortic coverage did not vary across cohorts, nor did procedural times or blood loss volume. Compliance with the SCI prevention protocol was 100% across both groups. Within the prophylactic drain cohort, one patient experienced an adverse event related to lumbar drain placement, manifested as an epidural hematoma requiring laminectomy, without neurologic deficit (n = 1/10; 10%). There was one SCI event (n = 1/20; 5%), which occurred in the prophylactic drain cohort on postoperative day 9 following an episode of hypotension related to a gastrointestinal bleed. CONCLUSIONS: The role of prophylactic CSF drains for the prevention of SCI following endovascular TAAA repair is a topic of ongoing research, with many current practices based on expert opinion and experience, rather than rigorous scientific data. This study demonstrates the feasibility of a multicenter randomized clinical trial to evaluate the role of prophylactic vs therapeutic CSF drains in the prevention of SCI in patients undergoing endovascular TAAA repair.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Drenagem , Procedimentos Endovasculares , Estudos de Viabilidade , Isquemia do Cordão Espinal , Humanos , Aneurisma da Aorta Torácica/cirurgia , Projetos Piloto , Procedimentos Endovasculares/efeitos adversos , Drenagem/efeitos adversos , Drenagem/instrumentação , Masculino , Estudos Prospectivos , Feminino , Idoso , Resultado do Tratamento , Implante de Prótese Vascular/efeitos adversos , Isquemia do Cordão Espinal/prevenção & controle , Isquemia do Cordão Espinal/etiologia , Pessoa de Meia-Idade , Fatores de Tempo , Aneurisma da Aorta Toracoabdominal
20.
Front Med (Lausanne) ; 11: 1361723, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601118

RESUMO

Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above. Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review. Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient. Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA