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Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.
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Histonas , Ácido Láctico , Microglia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Histonas/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Ácido Láctico/metabolismo , Ratos , Lisina/metabolismo , Lisina/análogos & derivados , Lisina/farmacologia , Camundongos , Cicatriz/metabolismo , Cicatriz/patologia , Feminino , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL , Masculino , Locomoção/efeitos dos fármacos , Locomoção/fisiologiaRESUMO
BACKGROUND: Essential tremor (ET) is a common debilitating condition, yet current treatments often fail to provide satisfactory relief. Transcutaneous spinal cord electrical stimulation (tSCS) has emerged as a potential noninvasive neuromodulation technique capable of disrupting the oscillatory activity underlying tremors. OBJECTIVE: This study aimed to investigate the potential of tSCS to disrupt tremor in a frequency-dependent manner in a cohort of patients with ET. METHODS: Eighteen patients with ET completed the study. The experiment consisted of 60-s postural tremor recording, during tSCS at tremor frequency, at 1 Hz, at 21 Hz, no stimulation, and trapezius stimulation. Tremor frequency and amplitude were analyzed and compared across the conditions. RESULTS: We found tremor amplitude reduction at tremor frequency stimulation significant only during the second half of the stimulation. The same stimulation resulted in the highest number of responders. tSCS at 1 Hz showed a trend toward decreased tremor amplitude in the latter half of stimulation. tSCS at 21 Hz did not produce any significant alterations in tremor, whereas trapezius stimulation exacerbated it. Notably, during tremor frequency stimulation, a subgroup of responders exhibited consistent synchronization between tremor phase and delivered stimulation, indicating tremor entrainment. CONCLUSIONS: Cervical tSCS holds promise for alleviating postural tremor in patients with ET when delivered at the subject's tremor frequency. The observed changes in tremor amplitude likely result from the modulation of spinal cord circuits by tSCS, which disrupts the oscillatory drive to muscles by affecting afferent pathways or spinal reflexes. However, the possibility of an interplay between spinal and supraspinal centers cannot be discounted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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The impact of primary and secondary injuries of spinal cord injury (SCI) results in the demise of numerous neurons, and there is still no efficacious pharmacological intervention for it. Recently, studies have shown that endoplasmic reticulum stress (ERS) plays a pivotal role in recovery of neurological function after spinal cord injury. As a process to cope with intracellular accumulation of misfolded and unfolded proteins which triggers ERS, the unfolded protein response (UPR) plays an important role in maintaining protein homeostasis. And, a recently disclosed small molecule AA147, which selectively activates activating transcription factor 6 (ATF6), has shown promising pharmacological effects in several disease models. Thus, it seems feasible to protect the neurons after spinal cord injury by modulating UPR. In this study, primary neurons were isolated from E17-19 C57BL/6J mouse embryos and we observed that AA147 effectively promoted the survival of neurons and alleviated neuronal apoptosis after oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. This was evident through a decrease in the proportion of PI-positive and TUNEL-positive cells, an increase in BCL-2 expression, and a decrease in the expression of BAX and C-caspase3. In in-vivo experiments, these findings were corroborated by TUNEL staining and immunohistochemistry. It was also found that AA147 enhanced three arms of the unfolded protein response with reduced CHOP expression. Besides, AA147 mitigated the accumulation of ROS in neurons probably by upregulating catalase expression. Furthermore, spinal cord injury models of C57BL/6J mice were established and behavioral experiments revealed that AA147 facilitated the recovery of motor function following SCI. Thus, pharmacologic activation of ATF6 represents a promise therapeutic approach to ameliorate the prognosis of SCI.
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Complex neurophysiological and morphologic experiments require suitable animal models for investigation. The rabbit is one of the most successful models for studying spinal cord functions owing to its substantial size. However, achieving precise surgical access to specific spinal regions requires a thorough understanding of the spinal cord's cytoarchitectonic structure and its spatial relationship with the vertebrae. The comprehensive anatomo-neurochemical atlases of the spinal cord are invaluable for attaining such insight. While such atlases exist for some rodents and primates, none exist for rabbits. We have developed a spinal cord atlas for rabbits to bridge this gap. Utilizing various neurochemical markers-including antibodies to NeuN, calbindin 28 kDa, parvalbumin, choline acetyltransferase, nitric oxide synthase, and non-phosphorylated heavy-chain neurofilaments (SMI-32 antibody)-we present the visualization of diverse spinal neuronal populations, various spinal cord metrics, stereotaxic maps of transverse slices for each spinal segment, and a spatial map detailing the intricate relationship between the spinal cord and the vertebrae across its entire length.
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Despite playing diverse physiological roles, the area surrounding the central canal, lamina X, remains one of the least studied spinal cord regions. Technical challenges and limitations of the commonly used experimental approaches are the main difficulties that hamper lamina X research. In the current protocol, we describe a reliable method for functional investigation of lamina X neurons that requires neither time-consuming slicing nor sophisticated in vivo experiments. Our approach relies on ex vivo hemisected spinal cord preparation that preserves the rostrocaudal and mediolateral spinal architecture as well as the dorsal roots, and infrared LED oblique illumination for visually guided patch clamp in thick blocks of tissue. When coupled with electric stimulation of the spared dorsal roots, electrophysiological recordings provide information on primary afferent inputs to lamina X neurons from myelinated and non-myelinated fibers and allow estimating primary afferent-driven presynaptic inhibition. Overall, we describe a simple, time-efficient, inexpensive, and versatile approach for lamina X research. Key features ⢠Quick and easy preparation procedure that grants access to lamina X neurons without spinal cord slicing ⢠Preserved rostrocaudal and mediolateral connectivity and preserved primary afferent supply ⢠Ability to perform electrophysiological recordings in combination with dorsal root stimulations allowing to study afferent inputs and presynaptic inhibition of lamina X neurons.
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This case report describes 2 patients with spinal cord schistosomiasis diagnosed based on a magnetic resonance imaging finding of a unique arborized type of postcontrast enhancement. Both patients presented with back pain and lower limb weakness, and prompt treatment with an anti-schistomal agent and steroid resulted in significant neurological and radiological improvement. The report emphasizes the role of imaging in the early diagnosis of spinal cord schistosomiasis, as well as the importance of early treatment for the best clinical outcomes.
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Asian seabass, Lates calcarifer, is one of the most important fish species in aquaculture. An attempt was made to develop a primary cell culture from the spinal cord of Lates calcarifer by the enzymatic and mechanical dissociation method. The primary cell culture was sub-cultured for 20 times in Leibovitz's L-15 medium with 20% fetal bovine serum (FBS) and 0.5 nM of human neurotrophin-3 at 28°C. The primary cell culture was cryopreserved at different passage levels and recovery of cells after long-term storage was estimated about 75-85%. The authenticity of origin of primary cell culture from L. calcarifer was confirmed by polymerase chain reaction assay using species-specific mitochondrial 12S rRNA primer. The primary cell culture was designated as seabass spinal cord cells (SBSC). The cells morphologically resembled the neurons due to their neural-like prolongations and star-like structure. Immunophenotypic analysis of the SBSC revealed that they are of neuronal origin. The SBSC were found to be highly susceptible to striped jack nervous necrosis virus (SJNNV) and infection in the cells was confirmed by RT-PCR. In conclusion, this is the first innovative euryhaline fish neuronal primary cell culture of L. calcarifer now available for neurophysiological and neurotoxicological studies.
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INTRODUCTION: The revised international standards for neurological classification of spinal cord injury (ISNCSCI) have facilitated the documentation of non-spinal cord injury-related impairments, such as chronic peripheral nerve injuries and muscle weakness due to immobility. This advancement addresses potential biases in muscle strength examinations. Utilizing electrically evoked contractions from paralyzed muscles, enhanced by electrodiagnosis, holds promise in identifying false-negative diagnoses of non-responsiveness to neuromuscular electrical stimulation. This concept prompts the exploration of polyneuromyopathy arising from nonuse in paralyzed muscles. CASE SERIES PRESENTATION: To substantiate our hypothesis, we recruited nine participants for a case series aimed at elucidating the potential benefits of incorporating the stimulus electrodiagnostic test (SET) to mitigate non-responsiveness during preparation for functional electrical stimulation (FES)-assisted cycling. In our convenience sample (n = 5), we conducted neurological mapping based on ISNCSCI and applied SET on the quadriceps. The SET guided optimal dosimetry for evoking contractions and revealed responses similar to those observed in peripheral neuropathies, with α coefficients equal to or lower than 2.00. This observation is likely attributable to nonuse of paralyzed muscles, indicative of an ongoing polyneuropathy in individuals with chronic spinal cord injury (SCI). DISCUSSION: Among the nine initially recruited subjects, seven exhibited responsiveness to neuromuscular electrical stimulation (78% responsiveness), with two participants excluded based on exclusion criteria. In the final five reported cases, all displayed α coefficient values indicating impaired neuromuscular accommodation, and one presented no α coefficient within the normal range. The inclusion of electrodiagnosis appears effective in averting non-responsiveness, suggesting the presence of ongoing polyneuropathies in paralyzed muscles.
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Eletrodiagnóstico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Polineuropatias/diagnóstico , Estimulação Elétrica , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/complicações , Eletromiografia , Contração Muscular/fisiologia , Debilidade Muscular/diagnóstico , Idoso , Músculo EsqueléticoRESUMO
The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.
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BACKGROUND: Inadequate nerve regeneration and an inhibitory local microenvironment are major obstacles to the repair of spinal cord injury (SCI). The activation and differentiation fate regulation of endogenous neural stem cells (NSCs) represent one of the most promising repair approaches. Metformin has been extensively studied for its antioxidative, anti-inflammatory, anti-aging, and autophagy-regulating properties in central nervous system diseases. However, the effects of metformin on endogenous NSCs remains to be elucidated. METHODS: The proliferation and differentiation abilities of NSCs were evaluated using CCK-8 assay, EdU/Ki67 staining and immunofluorescence staining. Changes in the expression of key proteins related to ferroptosis in NSCs were detected using Western Blot and immunofluorescence staining. The levels of reactive oxygen species, glutathione and tissue iron were measured using corresponding assay kits. Changes in mitochondrial morphology and membrane potential were observed using transmission electron microscopy and JC-1 fluorescence probe. Locomotor function recovery after SCI in rats was assessed through BBB score, LSS score, CatWalk gait analysis, and electrophysiological testing. The expression of the AMPK pathway was examined using Western Blot. RESULTS: Metformin promoted the proliferation and neuronal differentiation of NSCs both in vitro and in vivo. Furthermore, a ferroptosis model of NSCs using erastin treatment was established in vitro, and metformin treatment could reverse the changes in the expression of key ferroptosis-related proteins, increase glutathione synthesis, reduce reactive oxygen species production and improve mitochondrial membrane potential and morphology. Moreover, metformin administration improved locomotor function recovery and histological outcomes following SCI in rats. Notably, all the above beneficial effects of metformin were completely abolished upon addition of compound C, a specific inhibitor of AMP-activated protein kinase (AMPK). CONCLUSION: Metformin, driven by canonical AMPK-dependent regulation, promotes proliferation and neuronal differentiation of endogenous NSCs while inhibiting ferroptosis, thereby facilitating recovery of locomotor function following SCI. Our study further elucidates the protective mechanism of metformin in SCI, providing new mechanistic insights for its candidacy as a therapeutic agent for SCI.
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Proteínas Quinases Ativadas por AMP , Diferenciação Celular , Proliferação de Células , Ferroptose , Metformina , Células-Tronco Neurais , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Metformina/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Animais , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
BACKGROUND: The traumatic spinal cord injury (SCI) can cause immediate multi-faceted function loss or paralysis. Microglia, as one of tissue resident macrophages, has been reported to play a critical role in regulating inflammation response during SCI processes. And transplantation with M2 microglia into SCI mice promotes recovery of motor function. However, the M2 microglia can be easily re-educated and changed their phenotype due to the stimuli of tissue microenvironment. This study aimed to find a way to maintain the function of M2 microglia, which could exert an anti-inflammatory and pro-repair role, and further promote the repair of spinal cord injury. METHODS: To establish a standard murine spinal cord clip compression model using Dumont tying forceps. Using FACS, to sort microglia from C57BL/6 mice or CX3CR1GFP mice, and further culture them in vitro with different macrophage polarized medium. Also, to isolate primary microglia using density gradient centrifugation with the neonatal mice. To transfect miR-145a-5p into M2 microglia by Lipofectamine2000, and inject miR-145a-5p modified M2 microglia into the lesion sites of spinal cord for cell transplanted therapy. To evaluate the recovery of motor function in SCI mice through behavior analysis, immunofluorescence or histochemistry staining, Western blot and qRT-PCR detection. Application of reporter assay and molecular biology experiments to reveal the mechanism of miR-145a-5p modified M2 microglia therapy on SCI mice. RESULTS: With in vitro experiments, we found that miR-145a-5p was highly expressed in M2 microglia, and miR-145a-5p overexpression could suppress M1 while promote M2 microglia polarization. And then delivery of miR-145a-5p overexpressed M2 microglia into the injured spinal cord area significantly accelerated locomotive recovery as well as prevented glia scar formation and neuron damage in mice, which was even better than M2 microglia transplantation. Further mechanisms showed that overexpressed miR-145a-5p in microglia inhibited the inflammatory response and maintained M2 macrophage phenotype by targeting TLR4/NF-κB signaling. CONCLUSIONS: These findings indicate that transplantation of miR-145a-5p modified M2 microglia has more therapeutic potential for SCI than M2 microglia transplantation from epigenetic perspective.
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Camundongos Endogâmicos C57BL , MicroRNAs , Microglia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Microglia/metabolismo , CamundongosRESUMO
OBJECTIVE: To investigate the changes and clinical significance of NOD like receptor protein 3 (NLRP3) inflammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury (SCI). METHODS: Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group, There were 48 males and 38 females, with an average age of (43.48±6.58) years old. And 100 healthy volunteers who underwent physical examination during the same time were selected as control group, including 56 males patients and 44 females patients, with an average age of (45.13±6.43) years old. Peripheral blood mononuclear cell (PBMC) were collected, and the mRNA expressions of NLRP3 and Caspase-1 were detected. Serum was collected and the levels of interleukin (IL)- 1ß, IL-18 were detected. According to Frankel's grade, the SCI group was divided into complete injury patients and incomplete injury patients, and according to the Japanese Orthopedic Society (JOA) grade, the SCI group was divided into good prognosis group and poor prognosis group. The difference of NLRP3, Caspase-1, IL-1ß, IL-18 among groups were compared, the influencing factors for poor prognosis in SCI patients was analyzed by Logistic regression. RESULTS: The mRNA expression levels of NLRP3 (1.41±0.33) and Caspase-1 (1.44±0.35) in PBMC and the levels of IL-1ß(45.34±13.22) pg·ml-1, IL-18(40.95±8.77) pg·ml-1 in serum of SCI group were higher than those of the control group[(1.00±0.19), (1.00±0.16), (16.58±4.24) pg·ml-1, (12.57±3.68) pg·ml-1] (P<0.05). The mRNA expression levels of NLRP3(1.63±0.34) and Caspase-1 (1.67±0.27) in PBMC and the levels of IL-1ß(51.09±11.10) pg·ml-1, IL-18 (47.65±7.93) pg·ml-1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury [(1.31±0.27), (1.34±0.33), (42.85±13.36) pg·ml-1, (38.05±7.48) pg·ml-1](P<0.05). The mRNA expression levels of NLRP3 (1.66±0.31) and Caspase-1 (1.72±0.31)in PBMC and the levels of IL-1ß(51.21±11.31) pg·ml-1, IL-18 (45.70±7.25) pg·ml-1 in serum, the proportion of complete injury(21 patients), and the proportion of spinal cord edema or bleeding of patients(15 patients) with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26), (1.37±0.36), (42.79±13.25) pg·ml-1ã(38.90±8.63) pg·ml-1, 5ã20 cases](P<0.05). Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing factors for poor prognosis in the SCI group (P<0.05). CONCLUSION: The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis, and NLRP3 expression can serve as a marker for evaluating prognosis.
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Caspase 1 , Inflamassomos , Interleucina-18 , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Masculino , Feminino , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/sangue , Adulto , Pessoa de Meia-Idade , Interleucina-18/sangue , Interleucina-1beta/sangue , Interleucina-1beta/genética , Caspase 1/sangue , Fraturas da Coluna Vertebral/sangue , Fraturas da Coluna Vertebral/complicações , Leucócitos Mononucleares/metabolismo , Prognóstico , Relevância ClínicaRESUMO
The spatial segmental location of motoneurons in the human spinal cord is influenced by both evolutionary and functional principles tending to optimize motor control, reflex integration, and adaptation to the demands of movement. Bearing in mind the biomechanics of limb muscles, it is logical to examine how motoneuron activity clusters functionally during typical daily activities like walking. This article provides a summary of advancements in the study of spinal maps of motoneuron activation during human locomotion by reviewing data gathered over â¼20 years. The effects of child development, aging, and neurological disorders show the salient characteristics of spinal segmental activity during different human locomotor tasks and conditions. By exploiting the neuromechanics of the spinal motor circuits, that is, the link between motoneuron activity and gait mechanics, neuroprosthetics and other focused treatments may better help individuals with locomotor impairments.
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AIMS: To explore the role of voltage-gated calcium channels (VGCC) in 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5-hydroxy tryptamine (5-HT) 2A receptors and VGCCs in lumbosacral cord after SCI. METHODS: Female Sprague-Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS-EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS-EMG. Rats were euthanized and L6-S1 spinal cord were acquired for immunofluorescence. RESULTS: In SCI rats, intrathecal administration of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride or L-type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high-frequency oscillations. They could also prolong EUS bursting activity duration on EUS-EMG. Moreover, the effect of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride can be eliminated with the combined administration of L-type VGCC agonist, (±)-Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T-type VGCC blocker TTA-P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5-HT2A receptor and Cav1.2 immunolabeling-positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats. CONCLUSIONS: Our study demonstrated that 5-HT2A/2C agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride may improve SCI-induced DSD by inhibiting the L-type voltage-gated calcium channel in lumbosacral cord motoneurons.
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Canais de Cálcio Tipo L , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Feminino , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Ratos , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , AnfetaminasRESUMO
INTRODUCTION: Patient and public involvement (PPI) in research is an embedded practice in clinical research, however, its role in preclinical or laboratory-based research is less well established and presents specific challenges. This study aimed to explore the perspectives of two key stakeholder groups, preclinical researchers and clinicians on PPI in preclinical research, using spinal cord research as a case study. METHODS: Semi-structured interviews were conducted online with 11 clinicians and 11 preclinical researchers all working in the area of spinal cord injury (SCI). Interviews were transcribed verbatim and analysed thematically. FINDINGS: Nine themes were developed through analysis. Participants' perspectives included that people living with SCI had a right to be involved, that PPI can improve the relevance of preclinical research, and that PPI can positively impact the experiences of researchers. They identified the distance between lab-based research and the daily experiences of living with SCI to be a barrier and proactive management of accessibility and the motivated and networked SCI community as key facilitators. To develop strong partnerships, participants suggested setting clear expectations, ensuring good communication, and demonstrating respect for the time of PPI contributors involved in the research. CONCLUSIONS: While traditionally PPI has been more commonly associated with clinical research, participants identified several potential benefits of PPI in preclinical spinal cord research that have applicability to preclinical researchers more broadly. Preclinical spinal researchers should explore how to include PPI in their work. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers, and PPI facilitators collaborated as co-authors on the conceptualisation, design of the interview protocol, data analysis and writing of this manuscript.
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Entrevistas como Assunto , Participação do Paciente , Pesquisadores , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/terapia , Feminino , Masculino , Participação da Comunidade , Pesquisa Qualitativa , Adulto , Pesquisa Biomédica , Pessoa de Meia-IdadeRESUMO
Introduction: Upper limb function loss in cervical spinal cord injury (SCI) contributes to substantial disability, and negatively impacts quality of life. Nerve transfer and tendon transfer surgery can provide improved upper limb function. This study assessed the utilization of nerve and tendon transfer surgery for individuals with tetraplegia in Canada. Methods: Data from the Canadian Institute for Health Information's Discharge Abstracts Database and the National Ambulatory Care Reporting System were used to identify the nerve and tendon transfer procedures performed in individuals with tetraplegia (2004-2020). Cases were identified using cervical SCI ICD-10-CA codes and Canadian Classification of Intervention codes for upper extremity nerve and tendon transfers. Data on sex, age at time of procedure, province, and hospital stay duration were recorded. Results: From 2004 to 2020, there were ≤80 nerve transfer procedures (81% male, mean age 38.3 years) and 61 tendon transfer procedures (78% male, mean age 45.0 years) performed (highest in Ontario and British Columbia). Using an estimate of 50% eligibility, an average of 1.3% of individuals underwent nerve transfer and 1.0% underwent tendon transfer. Nerve transfers increased over time (2004-2009, n = <5; 2010-2015, n = 27; 2016-2019, n = 49) and tendon transfers remained relatively constant. Both transfer types were performed as day-surgery or single night stay. Conclusions: Nerve and tendon transfer surgery to improve upper limb function in Canadians with tetraplegia remains low. This study highlights a substantial gap in care for this vulnerable population. Identification of barriers that prevent access to care is required to promote best practice for upper extremity care.
Introduction : La perte de fonction du membre supérieur en cas de lésion de la moelle épinière cervicale (SCI0 contribue à un handicap substantiel avec des répercussions négatives sur la qualité de vie. La chirurgie de transfert des nerfs et des tendons peut apporter une amélioration du fonctionnement du membre supérieur. Cette étude a évalué l'utilisation de la chirurgie de transfert de nerfs et de tendons pour les patients tétraplégiques au Canada. Méthodes : Des données issues de la base de données des résumés de congés de l'Institut canadien d'information sur la santé du système national d'information sur les soins ambulatoires ont été utilisées pour identifier les procédures de transfert de nerfs et de tendons pratiquées sur des patients tétraplégiques entre 2004 et 2020. Les cas ont été identifiés en utilisant les codes de SCI cervicales du CIM-10-CA et des codes canadiens de classification des interventions pour les transferts de nerfs et de tendons du membre supérieur. Les données sur le sexe et l'âge au moment de la procédure, la province et la durée de séjour à l'hôpital ont été consignées. Résultats : Entre 2004 et 2020, il y a eu ≤ 80 procédures de transferts de nerfs (hommes : 81 %, âge moyen : 38,3 ans) et 61 procédures de transfert de tendons (hommes : 78 %, âge moyen : 45,0 ans) pratiquées (principalement en Ontario et en Colombie-Britannique). En estimant une admissibilité de 50 %, une moyenne de 1,3 % des patients a subi un transfert de nerfs et 1,0 % des patients a subi un transfert tendineux. Les transferts de nerfs ont augmenté au fil des années (2004-2009, n = < 5; 2010-2015, n = 27; 2016-2019, n = 49) tandis que le nombre de transferts tendineux est resté relativement stable. Les deux types de transferts ont été pratiqués das le cadre de la chirurgie d'un jour ou avec une hospitalisation d'une seule nuit. Conclusions : La chirurgie de transfert de nerfs et de tendons pour l'amélioration des fonctions des membres supérieurs reste peu utilisée pour les Canadiens tétraplégiques. Cette étude souligne une lacune substantielle des soins pour cette population vulnérable. Il est nécessaire d'identifier les obstacles qui empêchent l'accès aux soins afin de promouvoir une meilleure pratique pour les soins du membre supérieur.
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"State of the Art" Learning Objectives: This manuscript serves to provide the reader with a general overview of the contemporary approaches to peripheral nerve reconstruction as the field has undergone considerable advancement over the last 3 decades. The learning objectives are as follows: To provide the reader with a brief history of peripheral nerve surgery and some of the landmark developments that allow for current peripheral nerve care practices.To outline the considerations and management options for the care of patients with brachial plexopathy, spinal cord injury, and lower extremity peripheral nerve injury.Highlight contemporary surgical techniques to address terminal neuroma and phantom limb pain.Review progressive and future procedures in peripheral nerve care, such as supercharge end-to-side nerve transfers.Discuss rehabilitation techniques for peripheral nerve care.
Le présent manuscrit vise à fournir au lecteur un aperçu général des approches contemporaines de la reconstruction des nerfs périphériques puisque le domaine a beaucoup progressé depuis trois décennies. Les objectifs d'apprentissage s"établissent comme suit : Fournir au lecteur un bref historique de la chirurgie des nerfs périphériques et quelques-unes des avancées historiques qui ont donné lieu aux pratiques de soins actuelles des nerfs périphériques.Décrire les considérations et les possibilités de prise en charge pour les soins des patients ayant une plexopathie brachiale, une lésion médullaire ou une lésion des nerfs périphériques des membres inférieurs.Souligner les techniques chirurgicales contemporaines pour traiter les neurones terminaux et les douleurs des membres fantômes.Examiner les interventions progressives et futures pour les soins des nerfs périphériques, comme l'amplification du transfert du nerf terminal au nerf latéral.Parler des techniques de réadaptation pour les soins des nerfs périphériques.
RESUMO
Spinal cord infarction (SCI) is a rare vascular event accounting for 1% of all strokes. Neurological syndromes may vary according to the arterial territory involved. This condition may differ in onset, severity, and recovery, making it a diagnostic challenge for clinicians. Diagnosis is made on a clinical basis, and neuroimaging (magnetic resonance imaging (MRI)) provides confirmatory evidence. A 72-year-old male, with a medical history of being overweight, hyperuricemia, dyslipidemia, and cigarette smoking presented to our emergency department (ED) with sudden-onset leg weakness. He reported chest pain with radiation to the back, followed by sudden arm and leg weakness, evolving to inferior limb plegia within four hours. He also noticed a loss of sensation below the breast region. On admission, vital signs were stable. Neurological examination demonstrated paraplegia of inferior limbs with absent deep tendon reflexes. Both pinprick, vibrational, and proprioceptive sensitivities were absent below T6. A diagnostic workup revealed lactescent serum suggesting severe hypertriglyceridemia. A clinical diagnosis of spinal cord infarction was made, which was later confirmed with MRI demonstrating an acute ischemic lesion in the anterior spinal artery (ASA) with the "owl's eye" sign, from T5 with extension to the cone. Neurological examination remained unaltered. He started aspirin and insulin perfusion. Since spinal cord injury is an uncommon cause of paraplegia, physicians should be extremely cautious. Despite the results of magnetic resonance imaging, the clinical picture was not consistent, which was finally explained by perilesional edema. To our knowledge, this is a rare case combining SCI with hypertriglyceridemia. Notwithstanding the lack of evidence linking reducing triglyceride levels to neurological recovery, insulin infusion was carried out given the hazards associated with sustaining such high levels of triglycerides. We aim to emphasize some characteristic MRI findings and the wealth of possible etiologies contributing to this clinical entity.
RESUMO
The aim of the present study was to determine the relationship between dose of oxybutynin and reduction in detrusor pressure in individuals with neurogenic bladder (NGB) secondary to spinal cord injury (SCI). The hospital-based data were examined for all individuals with NGB and SCI who were admitted for urological evaluation between January 1999 and December 2016. Patient characteristics, urodynamics and bladder management details were collected at pre-treatment and post-treatment. The primary outcome used to assess oxybutynin treatment was the change in detrusor pressure (Pdet). Analysis of covariance (ANCOVA) was used to investigate the relationship between dosage of oxybutynin and decrease in Pdet. A total of 245 participants (112 who received no medication and 133 treated with oxybutynin) were included. After controlling for confounding factors, each 1 mg increase in oxybutynin was associated with a mean decrease of 0.9 cmH2O in Pdet (95% CI, -1.4 to -0.3). Stratifying bladder management by indwelling catheter, oxybutynin at a dose of 1 mg was associated with a mean decrease in Pdet of 0.5 cmH2O (95% CI, -1.4 to 0.4) in patients with indwelling catheters and 1.0 cmH2O (95% CI, -1.7 to -0.3) in patients with clean intermittent catheterization and balanced bladder. This study provided guidance for setting the starting dose of drugs associated with response variability in NGB with SCI. Oxybutynin is deemed to be clinically effective for managing NGB in patients with SCI.
RESUMO
Spinal cord injury (SCI) denotes damage to both the structure and function of the spinal cord, primarily manifesting as sensory and motor deficits caused by disruptions in neural transmission pathways, potentially culminating in irreversible paralysis. Its pathophysiological processes are complex, with numerous molecules and signaling pathways intricately involved. Notably, the pronounced upregulation of the Wnt signaling pathway post-SCI holds promise for neural regeneration and repair. Activation of the Wnt pathway plays a crucial role in neuronal differentiation, axonal regeneration, local neuroinflammatory responses, and cell apoptosis, highlighting its potential as a therapeutic target for treating SCI. However, excessive activation of the Wnt pathway can also lead to negative effects, highlighting the need for further investigation into its applicability and significance in SCI. This paper provides an overview of the latest research advancements in the Wnt signaling pathway in SCI, summarizing the recent progress in treatment strategies associated with the Wnt pathway and analyzing their advantages and disadvantages. Additionally, we offer insights into the clinical application of the Wnt signaling pathway in SCI, along with prospective avenues for future research direction.