Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43.402
Filtrar
1.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 34(1): 44-l47, ene.-feb. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-214413

RESUMO

A 10-year-old boy presented to neurosurgery department after a gunshot wound to the upper thoracic spine. The bullet entered through the right deltoid muscle and lodged inside the spinal canal at T1 level. The patient arrived conscious and obeying commands; however, he experienced a loss of sensation below T3 level, loss of reflexes below the injured T1 level, loss of anal sphincter tone and paraplegia in the lower limbs (American Spinal Injury Association grade-A). Imaging studies revealed an intra-canalicular metallic bullet at the T1 level. The patient underwent urgent operation using a tubular retractor system and the microscope. Subsequently, the bullet was successfully retrieved. Postoperatively, the patient made a significant recovery and by the end of the 6th month, he was able to walk independently despite some gait instability. A minimally invasive approach for intra-canalicular bullet removal in the thoracic region is a safe and effective technique in pediatric patients. (AU)


Un niño de 10 años se presentó al departamento de neurocirugía después de una herida de bala en la columna torácica superior. La bala entró por el músculo deltoides derecho y se alojó dentro del canal espinal a nivel T1. El paciente llegó consciente y obedeciendo órdenes; sin embargo, experimentó una pérdida de sensibilidad por debajo del nivel T3, pérdida de reflejos por debajo del nivel T1 lesionado, pérdida del tono del esfínter anal y paraplejía en las extremidades inferiores (American Spinal Injury Association grado-A). Los estudios de imagen revelaron una bala metálica intracanalicular a nivel T1. El paciente fue intervenido de urgencia mediante un sistema retractor tubular y el microscopio. Posteriormente, la bala se recuperó con éxito. En el postoperatorio, el paciente se recuperó significativamente y, al final del sexto mes, podía caminar de forma independiente a pesar de cierta inestabilidad en la marcha. Un enfoque mínimamente invasivo para la extracción de balas intracanaliculares en la región torácica es una técnica segura y eficaz en pacientes pediátricos. (AU)


Assuntos
Humanos , Masculino , Criança , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos/métodos , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/cirurgia , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/cirurgia , Resultado do Tratamento
2.
J Neuroinflammation ; 20(1): 6, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609266

RESUMO

Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the blood‒brain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the blood‒brain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.


Assuntos
Piroptose , Traumatismos da Medula Espinal , Camundongos , Animais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Lisossomos/metabolismo , Fosfolipases A2 Citosólicas/metabolismo
3.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614259

RESUMO

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.


Assuntos
Materiais Biocompatíveis , Traumatismos da Medula Espinal , Humanos , Materiais Biocompatíveis/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Medicina Regenerativa , Transplante de Células-Tronco , Regeneração Nervosa
4.
Oxid Med Cell Longev ; 2023: 1485135, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36686379

RESUMO

Background: Spinal cord injury (SCI) is known to cause a more robust systemic inflammatory response than general trauma without CNS injury, inducing severe secondary organ damage, especially the lung and liver. Related studies are principally focused on the mechanisms underlying repair and regeneration in the injured spinal cord tissue. However, the specific mechanism of secondary injury after acute SCI is widely overlooked, compared with general trauma. Methods: Two datasets of GSE151371 and GSE45376 related to the blood samples and spinal cord after acute SCI were selected to identify the differentially expressed genes (DEGs). In GSE151371, functional enrichment analysis on specific DEGs of blood samples was performed. And the top 15 specific hub genes were identified from intersectional genes between the specific upregulated DEGs of blood samples in GSE151371 and the upregulated DEGs of the spinal cord in GSE45376. The specific functional enrichment analysis and the drug candidates of the hub genes and the miRNAs-targeted hub genes were also analyzed and predicted. Results: DEGs were identified, and a total of 64 specific genes were the intersection of upregulated genes of the spinal cord in GSE45376 and upregulated genes of human blood samples in GSE151371. The top 15 hub genes including HP, LCN2, DLGAP5, CEP55, HMMR, CDKN3, PRTN3, SKA3, MPO, LTF, CDC25C, MMP9, NEIL3, NUSAP1, and CD163 were calculated from the 64 specific genes. Functional enrichment analysis of the top 15 hub genes revealed inflammation-related pathways. The predicted miRNAs-targeted hub genes and drug candidates of hub genes were also performed to put forward reasonable treatment strategies. Conclusion: The specific hub genes of acute SCI as compared with trauma without CNS injury were identified. The functional enrichment analysis of hub genes showed a specific immune response. Several predicted drugs of hub genes were also obtained. The hub genes and the predicted miRNAs may be potential biomarkers and therapeutic targets and require further validation.


Assuntos
MicroRNAs , Traumatismos da Medula Espinal , Humanos , Perfilação da Expressão Gênica , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , MicroRNAs/genética , Biomarcadores , Proteínas de Ciclo Celular/genética , Proteínas Associadas aos Microtúbulos/genética
5.
Neurosurgery ; 92(2): 353-362, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36637270

RESUMO

BACKGROUND: Decompression of the injured spinal cord confers neuroprotection. Compared with timing of surgery, verification of surgical decompression is understudied. OBJECTIVE: To compare the judgment of cervical spinal cord decompression using real-time intraoperative ultrasound (IOUS) following laminectomy with postoperative MRI and CT myelography. METHODS: Fifty-one patients were retrospectively reviewed. Completeness of decompression was evaluated by real-time IOUS and compared with postoperative MRI (47 cases) and CT myelography (4 cases). RESULTS: Five cases (9.8%) underwent additional laminectomy after initial IOUS evaluation to yield a final judgment of adequate decompression using IOUS in all 51 cases (100%). Postoperative MRI/CT myelography showed adequate decompression in 43 cases (84.31%). Six cases had insufficient bony decompression, of which 3 (50%) had cerebrospinal fluid effacement at >1 level. Two cases had severe circumferential intradural swelling despite adequate bony decompression. Between groups with and without adequate decompression on postoperative MRI/CT myelography, there were significant differences for American Spinal Injury Association motor score, American Spinal Injury Association Impairment Scale grade, AO Spine injury morphology, and intramedullary lesion length (IMLL). Multivariate analysis using stepwise variable selection and logistic regression showed that preoperative IMLL was the most significant predictor of inadequate decompression on postoperative imaging (P = .024). CONCLUSION: Patients with severe clinical injury and large IMLL were more likely to have inadequate decompression on postoperative MRI/CT myelography. IOUS can serve as a supplement to postoperative MRI/CT myelography for the assessment of spinal cord decompression. However, further investigation, additional surgeon experience, and anticipation of prolonged swelling after surgery are required.


Assuntos
Medula Cervical , Lesões do Pescoço , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Laminectomia/métodos , Projetos Piloto , Mielografia , Medula Cervical/cirurgia , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/cirurgia , Descompressão Cirúrgica/métodos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Lesões do Pescoço/cirurgia , Traumatismos da Coluna Vertebral/cirurgia , Resultado do Tratamento
6.
J Neuroeng Rehabil ; 20(1): 10, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681852

RESUMO

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort. METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves. RESULTS: Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY. CONCLUSIONS: The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Traumatismos da Medula Espinal , Humanos , Estudos Prospectivos , Caminhada
7.
J Orthop Surg Res ; 18(1): 60, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683024

RESUMO

BACKGROUND: Recent pieces of evidence about the efficacy of gait rehabilitation for incomplete spinal cord injury remain unclear. We aimed to estimate the treatment effect and find the best gait rehabilitation to regain velocity, distance, and Walking Index Spinal Cord Injury (WISCI) among incomplete spinal cord injury patients. METHOD: PubMed and Scopus databases were searched from inception to October 2022. Randomized controlled trials (RCTs) were included in comparison with any of the following: conventional physical therapy, treadmill, functional electrical stimulation and robotic-assisted gait training, and reported at least one outcome. Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed using random-effects or fixed-effect model according to the heterogeneity. Network meta-analysis (NMA) was indirectly compared with all interventions and reported as pooled unstandardized mean difference (USMD) and 95% confidence interval (CI). Surface under the cumulative ranking curve (SUCRA) was calculated to identify the best intervention. RESULTS: We included 17 RCTs (709 participants) with the mean age of 43.9 years. Acute-phase robotic-assisted gait training significantly improved the velocity (USMD 0.1 m/s, 95% CI 0.05, 0.14), distance (USMD 64.75 m, 95% CI 27.24, 102.27), and WISCI (USMD 3.28, 95% CI 0.12, 6.45) compared to conventional physical therapy. In NMA, functional electrical stimulation had the highest probability of being the best intervention for velocity (66.6%, SUCRA 82.1) and distance (39.7%, SUCRA 67.4), followed by treadmill, functional electrical stimulation plus treadmill, robotic-assisted gait training, and conventional physical therapy, respectively. CONCLUSION: Functional electrical stimulation seems to be the best treatment to improve walking velocity and distance for incomplete spinal cord injury patients. However, a large-scale RCT is required to study the adverse events of these interventions. TRIAL REGISTRATION: PROSPERO number CRD42019145797.


Assuntos
Marcha , Traumatismos da Medula Espinal , Humanos , Adulto , Metanálise em Rede , Marcha/fisiologia , Caminhada/fisiologia , Terapia por Exercício
8.
Sci Rep ; 13(1): 82, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596827

RESUMO

In primates, neurons giving rise to the corticospinal tract (CST) are distributed in several motor-related areas of the frontal lobe, such as the primary motor cortex (M1), the supplementary motor area (SMA), and the dorsal and ventral divisions of the premotor cortex (PMd, PMv). Recently, we have shown in macaque monkeys that the morphology of basal dendrites of CST neurons, i.e., large layer V pyramidal neurons, varies among the digit regions of the motor-related areas. Here, we investigated the alterations in basal dendrite morphology of CST neurons after spinal cord injury (SCI). In our monkey model, both the complexity and the spine density of basal dendrites were highly decreased throughout the areas. Notably, these events were less prominent for the PMd than for the M1, SMA, and PMv. In analyzing the density changes post-SCI of the filopodia-, thin-, stubby-, and mushroom-type spines, it was found that the density of filopodia-type spines was increased for all areas, whereas the other types of spines exhibited density decreases. Such spine density reductions were so limited for the PMd as compared to the other areas. The observed plastic changes of CST neurons may contribute to the recovery from impaired motor functions caused by SCI.


Assuntos
Córtex Motor , Traumatismos da Medula Espinal , Animais , Córtex Motor/fisiologia , Macaca , Haplorrinos , Neurônios/fisiologia , Primatas , Células Piramidais , Tratos Piramidais/fisiologia
9.
Neurocirugia (Astur : Engl Ed) ; 34(1): 44-47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36623892

RESUMO

A 10-year-old boy presented to neurosurgery department after a gunshot wound to the upper thoracic spine. The bullet entered through the right deltoid muscle and lodged inside the spinal canal at T1 level. The patient arrived conscious and obeying commands; however, he experienced a loss of sensation below T3 level, loss of reflexes below the injured T1 level, loss of anal sphincter tone and paraplegia in the lower limbs (American Spinal Injury Association grade-A). Imaging studies revealed an intra-canalicular metallic bullet at the T1 level. The patient underwent urgent operation using a tubular retractor system and the microscope. Subsequently, the bullet was successfully retrieved. Postoperatively, the patient made a significant recovery and by the end of the 6th month, he was able to walk independently despite some gait instability. A minimally invasive approach for intra-canalicular bullet removal in the thoracic region is a safe and effective technique in pediatric patients.


Assuntos
Traumatismos da Medula Espinal , Ferimentos por Arma de Fogo , Masculino , Humanos , Criança , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/cirurgia , Paraplegia/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , Procedimentos Neurocirúrgicos , Canal Medular/diagnóstico por imagem , Canal Medular/cirurgia
11.
Adv Exp Med Biol ; 1394: 137-152, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587386

RESUMO

The CNS tumors, in particular those with malignant characteristics, are prominent burdens around the world with high mortality and low cure rate. Given that, researchers were curious about novel treatments with promising effectiveness which resulted in shifting the dogmatism era of neurogenesis to the current concept of postnatal neurogenesis. Considering all existing stem cells, various strategies are available for treating CNS cancers, including hematopoietic stem cells transplantation, mesenchymal stem cells transplantation, neural stem cells (NSCs) transplantation, and using stem cells as genetic carriers called "suicide gene therapy". Despite some complications, this ongoing therapeutic method has succeeded in decreasing tumor volume, inhibiting tumor progression, and enhancing patients' survival. These approaches could lead to acceptable results, relatively better safety, and tolerable side effects compared to conventional chemo and radiotherapy. Accordingly, this treatment will be applicable to a wide range of CNS tumors in the near future. Furthermore, tumor genomic analysis and understanding of the underlying molecular mechanisms will help researchers determine patient selection criteria for targeted gene therapy.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Neurais , Traumatismos da Medula Espinal , Neoplasias da Medula Espinal , Humanos , Encéfalo , Células-Tronco Neurais/transplante , Terapia Genética/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Neoplasias da Medula Espinal/terapia , Traumatismos da Medula Espinal/terapia , Medula Espinal
12.
Sci Rep ; 13(1): 654, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635338

RESUMO

Scientists are concerned that the research they conduct accurately portrays the needs of people living with spinal cord injuries (SCI). As such, this study set out to investigate the main problems faced by people with SCI and their expectations for research. This quantitative, exploratory, analytical, and cross-sectional study was carried out online, with a non-probabilistic sample of 618 Brazilian adults with SCI who had registered voluntarily to participate in the research of the Neurorehab group. The virtual questionnaire consisted of 22 questions based on ISCOS Data Sets. The majority (68.9%) of participants were male, with higher education or a post-graduate qualification (49.5%). Most injuries had experienced traumatic injuries (78.5%) and 58.7% were paraplegic. The mean age was 38.04 years (SD = 9.85). The main difficulties faced after SCI were locomotion/accessibility (70.9%), neurogenic bladder (68.8%), neurogenic bowel (48.2%), and sexuality (36.1%). The highest demand was for experimental studies on stem cells (22.5%), rehabilitation (14.2%), and cures (13.9%). Most (84.3%) of those who reported sexuality problems after SCI were men (p = 0.013). The findings obtained empower people with SCI by enabling them to influence the agenda of scientific research based on their expectations and difficulties. This survey will also aid organizations to engage stakeholders to implement a comprehensive SCI management program.


Assuntos
Traumatismos da Medula Espinal , Adulto , Humanos , Masculino , Feminino , Brasil/epidemiologia , Estudos Transversais , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/reabilitação , Pesquisa , Inquéritos e Questionários
13.
J Neuroeng Rehabil ; 20(1): 3, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635693

RESUMO

BACKGROUND: In recent years, non-invasive brain stimulation (NIBS) has been used for motor function recovery. However, the effects of NIBS in populations with spinal cord injury (SCI) remain unclear. This study aims to conduct a meta-analysis of the existing evidence on the effects and safety of NIBS against sham groups for motor dysfunction after SCI to provide a reference for clinical decision-making. METHODS: Two investigators systematically screened English articles from PubMed, MEDLINE, Embase, and Cochrane Library for prospective randomized controlled trials regarding the effects of NIBS in motor function recovery after SCI. Studies with at least three sessions of NIBS were included. We assessed the methodological quality of the selected studies using the evidence-based Cochrane Collaboration's tool. A meta-analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: A total of 14 randomized control trials involving 225 participants were included. Nine studies used repetitive transcranial magnetic stimulation (rTMS) and five studies used transcranial direct current stimulation (tDCS). The meta-analysis showed that NIBS could improve the lower extremity strength (SMD = 0.58, 95% CI = 0.02-1.14, P = 0.004), balance (SMD = 0.64, 95% CI = 0.05-1.24, P = 0.03), and decrease the spasticity (SMD = - 0.64, 95% CI = - 1.20 to - 0.03, P = 0.04). However, the motor ability of the upper extremity in the NIBS groups was not statistically significant compared with those in the control groups (upper-extremity strength: P = 0.97; function: P = 0.56; and spasticity: P = 0.12). The functional mobility in the NIBS groups did not reach statistical significance when compared with the sham NIBS groups (sham groups). Only one patient reported seizures that occurred during stimulation, and no other types of serious adverse events were reported. CONCLUSION: NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity. Further high-quality clinical trials are needed to support or refute the use and optimize the stimulation parameters of NIBS in clinical practice.


Assuntos
Traumatismos da Medula Espinal , Estimulação Transcraniana por Corrente Contínua , Humanos , Estudos Prospectivos , Estimulação Magnética Transcraniana , Traumatismos da Medula Espinal/terapia , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Encéfalo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Fluids Barriers CNS ; 20(1): 1, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624478

RESUMO

BACKGROUND: Our previous study demonstrated that M1 macrophages could impair tight junctions (TJs) between vascular endothelial cells by secreting interleukin-6 (IL-6) after spinal cord injury (SCI). Tocilizumab, as a humanized IL-6 receptor (IL-6R) monoclonal antibody approved for the clinic, has been applied in the treatment of neurological diseases in recent years, but the treatment effect of Tocilizumab on the TJs restoration of the blood-spinal cord barrier (BSCB) after SCI remains unclear. This study aimed to explore the effect of Tocilizumab on the restoration of TJs between vascular endothelial cells and axon regeneration after SCI. METHODS: In this study, the mouse complete spinal cord crush injury model was used, and Tocilizumab was continuously injected intrathecally until the day of sample collection. A PBS injection in the same location was included as a control. At 14 days postinjury (dpi) and 28 dpi, spinal cord tissue sections were examined via tissue immunofluorescence. The Basso Mouse Scale (BMS) scores and footprint analysis were used to verify the effect of Tocilizumab on the recovery of motor function in mice after SCI. RESULTS: We demonstrated that depletion of macrophages has no effect on axon regeneration and motor functional recovery after SCI, but mice subjected to Tocilizumab showed a significant increase in axon regeneration and a better recovery in motor function during the chronic phase after SCI. Moreover, our study demonstrated that at 14 and 28 dpi, the expression of claudin-5 (CLDN5) and zonula occludens-1 (ZO-1) between vascular endothelial cells was significantly increased and the leakage of BSCB was significantly reduced in the injured core after daily intrathecal injection of Tocilizumab. Notably, the infiltration of CD68+ macrophages/microglia and the formation of fibrotic scar were decreased in the injured core after Tocilizumab treatment. Tocilizumab treatment could effectively reduce the IL-6 expression in macrophages in the injured core. CONCLUSION: The application of Tocilizumab to antagonize IL-6R can effectively reduce the expression of IL-6 in macrophages and facilitate TJs restoration of the BSCB, which is beneficial for axon regeneration and motor functional recovery after SCI. Hence, Tocilizumab treatment is a potential therapeutic strategy for SCI.


Assuntos
Traumatismos da Medula Espinal , Junções Íntimas , Camundongos , Animais , Junções Íntimas/metabolismo , Axônios/metabolismo , Células Endoteliais/metabolismo , Interleucina-6/farmacologia , Regeneração Nervosa , Traumatismos da Medula Espinal/metabolismo
15.
Spine (Phila Pa 1976) ; 48(3): 213-222, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607628

RESUMO

STUDY DESIGN: A functional, transcriptome, and long noncoding RNAs (lncRNAs) expression analysis in the spinal cord of mice after hyperbaric oxygen (HBO) treatment. OBJECTIVE: We aimed to explore the mechanism by which HBO treats spinal cord injury (SCI) at the level of lncRNAs. SUMMARY OF BACKGROUND DATA: Immense amounts of research have established that HBO treatment promotes the recovery of neurological function after SCI. The mechanism of action remains to be clarified. METHODS: High-throughput RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to profile lncRNA expression and analyze biological function in the spinal cords of mice from sham-operated, SCI, and HBO-treated groups. The differential expression of lncRNA between the groups was assessed using real-time quantitative polymerase chain reaction. RESULTS: Differential expression across 577 lncRNAs was identified among the three groups. GO analysis showed that free ubiquitin chain polymerization, ubiquitin homeostasis, DNA replication, synthesis of RNA primer, single-stranded telomeric DNA binding, and alpha-amylase activity were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis displayed that vitamin B6 metabolism, one carbon pool by folate, DNA replication, lysine degradation, beta-alanine metabolism, fanconi anemia pathway, and Notch signal pathway were the main pathways with enrichment significance. LncRNAs NONMMUT 092674.1, NONMMUT042986.2, and NONMMUT018850.2 showed significantly different expression between the SCI and the other two groups (P<0.05, <0.01). CONCLUSIONS: This study is the first to determine the expression profiles of lncRNAs in the injured spinal cord after HBO treatment. We identified several important dysregulated lncRNAs in this setting. These results help us better understand the mechanism by which HBO treats SCI and provide new potential therapeutic targets for SCI.


Assuntos
Oxigenoterapia Hiperbárica , RNA Longo não Codificante , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Oxigenoterapia Hiperbárica/métodos , Oxigênio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Medula Espinal , Ubiquitinas/genética , Ubiquitinas/metabolismo , Perfilação da Expressão Gênica
16.
Sci Transl Med ; 15(677): eabq6885, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599003

RESUMO

Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF-MAP2K signaling plays a key role in axon elongation during nervous system development. Here, we show that conditional expression of a constitutively kinase-activated BRAF in mature corticospinal neurons elicited the expression of a set of transcription factors previously implicated in the regeneration of zebrafish retinal ganglion cell axons and promoted regeneration and sprouting of corticospinal tract (CST) axons after spinal cord injury in mice. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, resulting in improved recovery of motor function. Noninvasive suprathreshold high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) activated the BRAF canonical downstream effectors MAP2K1/2 and modulated the expression of a set of regeneration-related transcription factors in a pattern consistent with that induced by BRAF activation. HF-rTMS enabled CST axon regeneration and sprouting, which was abolished in MAP2K1/2 conditional null mice. These data collectively demonstrate a central role of MAP2K signaling in augmenting the growth capacity of mature corticospinal neurons and suggest that HF-rTMS might have potential for treating spinal cord injury by modulating MAP2K signaling.


Assuntos
Axônios , Traumatismos da Medula Espinal , Animais , Camundongos , Axônios/fisiologia , Engenharia Genética , Regeneração Nervosa/fisiologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Tratos Piramidais/metabolismo , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Estimulação Magnética Transcraniana , Fatores de Transcrição/metabolismo , Peixe-Zebra
17.
Stem Cell Res Ther ; 14(1): 6, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36627662

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most frequent non-traumatic neurological debilitating disease among young adults with no cure. Over recent decades, efforts to treat neurodegenerative diseases have shifted to regenerative cell therapy. Adipose tissue-derived stromal vascular fraction (SVF) comprises a heterogeneous cell population, considered an easily accessible source of MSCs with therapeutic potential in autoimmune diseases. This study aimed to assess the regenerative capacity of low-level laser-activated SVF in an MS cat model. METHODS: Fifteen adult Persian cats were used in this study: Group I (control negative group, normal cats), Group II (EB-treated group, induced for MS by ethidium bromide (EB) intrathecal injection), and Group III (SVF co-treated group, induced for MS then treated with SVF on day 14 post-induction). The SVF was obtained after digesting the adipose tissue with collagenase type I and injecting it intrathecal through the foramen magnum. RESULTS: The results showed that the pelvic limb's weight-bearing locomotion activity was significantly (P ≤ 0.05) recovered in Group III, and the Basso, Beattie, and Bresnahan (BBB) scores of hindlimb locomotion were significantly higher in Group III (14 ± 0.44) than Group II (4 ± 0.31). The lesion's extent and intensity were reduced in the magnetic resonance imaging (MRI) of Group III. Besides, the same group showed a significant increase in the expression of neurotrophic factors: BDNF, SDF and NGF (0.61 ± 0.01, 0.51 ± 0.01 and 0.67 ± 0.01, respectively) compared with Group II (0.33 ± 0.01, 0.36 ± 0.006 and 0.2 ± 0.01, respectively). Furthermore, SVF co-treated group revealed a significant (P ≤ 0.05) increase in oligodendrocyte transcription factor (Olig2) and myelin basic protein (4 ± 0.35 and 6 ± 0.45, respectively) that was decreased in group II (1.8 ± 0.22 and 2.9 ± 0.20, respectively). Moreover, group III showed a significant (P ≤ 0.05) reduction in Bax and glial fibrillary acidic protein (4 ± 0.53 and 3.8 ± 0.52, respectively) as compared with group II (10.7 ± 0.49 and 8.7 ± 0.78, respectively). The transmission electron microscopy demonstrated regular more compact, and markedly (P ≤ 0.05) thicker myelin sheaths (mm) in Group III (0.3 ± 0.006) as compared with group II (0.1 ± 0.004). Based on our results, the SVF co-treated group revealed remyelination and regeneration capacity with a reduction in apoptosis and axonal degeneration. CONCLUSION: SVF is considered an easy, valuable, and promising therapeutic approach for treating spinal cord injuries, particularly MS.


Assuntos
Esclerose Múltipla , Traumatismos da Medula Espinal , Gatos , Animais , Esclerose Múltipla/terapia , Fração Vascular Estromal , Traumatismos da Medula Espinal/terapia , Tecido Adiposo , Células Estromais
18.
Theranostics ; 13(2): 810-832, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632211

RESUMO

Background: Caloric restriction mimetics (CRMs) mimic the favourable effects of caloric restriction (CR) and have been shown to have therapeutic effects in neuroinflammatory disease. However, whether CRMs improve the functional recovery from spinal cord injury (SCI) and the underlying mechanism of action remain unclear. In this study, we used the CRMs 3,4-dimethoxychalcone (3,4-DC) to evaluate the therapeutic value of CRMs for SCI. Methods: HE, Masson and Nissl staining; footprint analysis; and the Basso mouse scale were used to determine the functional recovery from SCI after 3,4-DC treatment. RNA sequencing was used to identify the mechanisms of 3,4-DC in SCI. Western blotting, qPCR and immunofluorescence were used to detect the levels of pyroptosis, necroptosis, autophagy and the AMPK-TRPML1-calcineurin signalling pathway. We employed a dual-luciferase reporter assay in vitro and applied AAV vectors to inhibit TFEB in vivo to explore the mechanism of 3,4-DC. Results: 3,4-DC reduced glial scar area and motor neuron death and improved functional recovery after SCI. RNA-sequencing results indicated that oxidative stress, pyroptosis, necroptosis, and autophagy may be involved in the ability of 3,4-DC to improve functional recovery. Furthermore, 3,4-DC inhibited pyroptosis and necroptosis by enhancing autophagy. We also found that 3,4-DC enhances autophagy by promoting TFEB activity. A decrease in the TFEB level abolished the protective effect of 3,4-DC. In addition, 3,4-DC partially regulated TFEB activity through the AMPK-TRPML1-calcineurin signalling pathway. Conclusions: 3,4-DC promotes functional recovery by upregulating TFEB-mediated autophagy and inhibiting pyroptosis and necroptosis after SCI, which may have potential clinical application value.


Assuntos
Piroptose , Traumatismos da Medula Espinal , Camundongos , Animais , Restrição Calórica , Necroptose , Proteínas Quinases Ativadas por AMP/farmacologia , Calcineurina , Traumatismos da Medula Espinal/metabolismo , Autofagia
19.
Theranostics ; 13(2): 849-866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632224

RESUMO

Background: Increasing evidence suggests that acute traumatic spinal cord injury (SCI)-induced defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following injury. Recently, Kruppel-like factor 2 (KLF2) was reported as a key molecular switch on regulating autophagy. Whether KLF2 coordinates endothelial endothelial ALP in SCI is not known. Methods: Genetic manipulations of KLF2 were performed in bEnd.3 cells and SCI model. Western blot, qRT-PCR, immunofluorescence staining and Lyso-Tracker Red staining, Evans blue dye extravasation, behavioral assessment via Basso mouse scale (BMS), electrophysiology and footprint analysis were performed. Results: In SCI, autophagy flux disruption in endothelial cells contributes to TJ proteins degradation, leading to blood-spinal cord barrier (BSCB) impairment. Furthermore, the KLF2 level was decreased in SCI, overexpression of which alleviated TJ proteins loss and BSCB damage, which improve motor function recovery in SCI mice, while knockdown of KLF2 displayed the opposite effects. At the molecular level, KLF2 overexpression alleviated the TJ proteins degradation and the endothelial permeability by tuning the ALP dysfunction caused by SCI and oxygen glucose deprivation (OGD). Conclusions: Endothelial KLF2 as one of the key contributors to SCI-mediated ALP dysfunction and BSCB disruption. KLF2 could be a promising pharmacological target for the management and treatment of SCI.


Assuntos
Células Endoteliais , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Células Endoteliais/metabolismo , Recuperação de Função Fisiológica , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Barreira Hematoencefálica/metabolismo , Fatores de Transcrição/metabolismo , Autofagia , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
20.
J Neural Eng ; 20(1)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36595241

RESUMO

Objective.Spinal cord neuromodulation has gained much attention for demonstrating improved motor recovery in people with spinal cord injury, motivating the development of clinically applicable technologies. Among them, transcutaneous spinal cord stimulation (tSCS) is attractive because of its non-invasive profile. Many tSCS studies employ a high-frequency (10 kHz) carrier, which has been reported to reduce stimulation discomfort. However, these claims have come under scrutiny in recent years. The purpose of this study was to determine whether using a high-frequency carrier for tSCS is more comfortable at therapeutic amplitudes, which evoke posterior root-muscle (PRM) reflexes.Approach.In 16 neurologically intact participants, tSCS was delivered using a 1 ms long monophasic pulse with and without a high-frequency carrier. Stimulation amplitude and pulse duration were varied and PRM reflexes were recorded from the soleus, gastrocnemius, and tibialis anterior muscles. Participants rated their discomfort during stimulation from 0 to 10 at PRM reflex threshold.Main Results.At PRM reflex threshold, the addition of a high-frequency carrier (0.87 ± 0.2) was equally comfortable as conventional stimulation (1.03 ± 0.18) but required approximately double the charge to evoke the PRM reflex (conventional: 32.4 ± 9.2µC; high-frequency carrier: 62.5 ± 11.1µC). Strength-duration curves for tSCS with a high-frequency carrier had a rheobase that was 4.8× greater and a chronaxie that was 5.7× narrower than the conventional monophasic pulse, indicating that the addition of a high-frequency carrier makes stimulation less efficient in recruiting neural activity in spinal roots.Significance.Using a high-frequency carrier for tSCS is equally as comfortable and less efficient as conventional stimulation at amplitudes required to stimulate spinal dorsal roots.


Assuntos
Traumatismos da Medula Espinal , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Medula Espinal/fisiologia , Raízes Nervosas Espinhais/fisiologia , Músculo Esquelético/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...