Very few reports have described giant pseudomeningoceles ≥ 8 cm in diameter. We report this case of the biggest giant pseudomeningocele at the unusual cervicothoracic level. A 59 year old man who underwent cervicotho...Very few reports have described giant pseudomeningoceles ≥ 8 cm in diameter. We report this case of the biggest giant pseudomeningocele at the unusual cervicothoracic level. A 59 year old man who underwent cervicothoracic laminectomy had a giant pseudomeningocele detected and the lesion gradually grew to about 15 cm in diameter by 2 years postoperatively. Cerebrospinal fluid leak closure was performed and the postoperative course was favorable. We present this case, review the literature and discuss the size and portion, mechanism of formation, symptoms and treatments of giant pseudomeningocele.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
BACKGROUND Administering anti-osteoporotic agents to patients perioperatively is a widely accepted approach for improving bone fusion rates and reducing the risk of complications.The best anti-osteoporotic agents for ...BACKGROUND Administering anti-osteoporotic agents to patients perioperatively is a widely accepted approach for improving bone fusion rates and reducing the risk of complications.The best anti-osteoporotic agents for spinal fusion surgery remain unclear.AIM To investigate the efficacy and safety of different anti-osteoporotic agents in spinal fusion surgery via network meta-analysis.METHODS Searches were conducted in four electronic databases(PubMed,EMBASE),Web of Science,the Cochrane Library and China National Knowledge Infrastructure(CNKI)from inception to November 2022.Any studies that compared antiosteoporotic agents vs placebo for spinal fusion surgery were included in this network meta-analysis.Outcomes included fusion rate,Oswestry disability index(ODI),and adverse events.Network meta-analysis was performed by R software with the gemtc package.RESULTS In total,13 randomized controlled trials were included in this network metaanalysis.Only teriparatide(OR 3.2,95%CI:1.4 to 7.8)was more effective than placebo in increasing the fusion rate.The surface under the cumulative ranking curve(SUCRA)of teriparatide combined with denosumab was the highest(SUCRA,90.9%),followed by teriparatide(SUCRA,74.0%),zoledronic acid(SUCRA,43.7%),alendronate(SUCRA,41.1%)and risedronate(SUCRA,35.0%).Teriparatide(MD-15,95%CI:-28 to-2.7)and teriparatide combined with denosumab(MD-20,95%CI:-40 to-0.43)were more effective than placebo in decreasing the ODI.The SUCRA of teriparatide combined with denosumab was highest(SUCRA,90.8%),followed by teriparatide(SUCRA,74.5%),alendronate(SURCA,52.7),risedronate(SURCA,52.1%),zoledronic acid(SURCA,24.2%)and placebo(SURCA,5.6%)for ODI.The adverse events were not different between groups.CONCLUSION This network meta-analysis suggests that teriparatide combined with denosumab and teriparatide alone significantly increase the fusion rate and decrease the ODI without increasing adverse events.Based on current evidence,teriparatide combined with denosumab or teriparatide alone is recommended to increase the fusion rate and to reduce ODI in spinal fusion patients.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained...Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained a penetrating cervical spinal cord injury from a sharpened stick.While initially tetraparetic,he rapidly recovered function.The risks of neurological deterioration during surgical removal made the patient reluctant to consent to surgery despite the impalement of the spinal cord.A repeat MRI on day 3 showed an extension of edema indicating progressive inflammation.On the 7~(th)day after injury,fever and paresthesias occurred with a large increase in serum inflammatory indicators,and the patient agreed to undergo surgical removal of the wooden object.We discuss the management nuances related to wood,the longitudinal evolution of MRI findings,infection risk,surgical risk mitigation and technique,an inflammatory marker profile,long-term recovery,and the surprisingly minimal neurological deficits associated with low-velocity midline spinal cord injuries.The patient had an excellent clinical outcome.The main lessons are that a wooden penetrating central nervous system injury has a high risk for infection,and that surgical removal from the spinal cord should be performed soon after injury and under direct visualization.展开更多
Objective: With the aging population and changes in lifestyle, lumbar spinal stenosis has become a common spinal disorder. Treatment modalities have been advancing, and the application of Enhanced Recovery After Surge...Objective: With the aging population and changes in lifestyle, lumbar spinal stenosis has become a common spinal disorder. Treatment modalities have been advancing, and the application of Enhanced Recovery After Surgery (ERAS) principles provides a new approach to postoperative recovery in patients. This study aims to investigate the clinical application effects of ERAS principles in single-level lumbar spinal stenosis surgery. Methods: This study included 64 patients who underwent lumbar fusion surgery in the Spinal Surgery Department of Baise People’s Hospital from July 2022 to July 2024. These patients were divided into an experimental group (ERAS group, 33 cases) and a control group (conventional group, 31 cases) based on perioperative care, receiving ERAS principles and traditional treatment, respectively. A comparison was made between the two groups in terms of gender, age, BMI, intraoperative blood loss, postoperative length of hospital stay, postoperative complications, hospital costs, VAS scores (preoperative/postoperative day 3), and ODI scores (preoperative/postoperative day 3). Results: There were no significant differences in gender, age, and BMI between the ERAS group and the conventional group (gender: χ2 = 0.5008, P = 0.4792;age: 54.55 ± 8.51 years vs. 57.39 ± 8.16 years, P = 0.0892;BMI: 25.11 ± 2.70 vs. 24.77 ± 2.75, P = 0.3098). However, during surgery, patients in the ERAS group had significantly less blood loss than those in the conventional group (197.58 ± 195.51ml vs. 438.71 ± 349.22 ml, P = 0.0006), and the postoperative length of hospital stay was significantly shorter (7.00 ± 2.24 days vs. 11.55 ± 5.23 days, P = 0.0000). On postoperative day 3, VAS scores were significantly better in the ERAS group compared to the conventional group (3.70 ± 0.88 vs. 4.32 ± 0.87, P = 0.0031), and the ODI scores showed significant improvement as well (46.00 ± 3.04 vs. 48.00 ± 3.39, P = 0.0078). Although there were no significant differences in postoperative complications and hospital costs (complications: 3 cases vs. 0 cases, P = 0.2154;hospital costs: 63524.29 ± 17891.80 RMB vs. 58733.84 ± 13280.82 RMB, P = 0.1154), ERAS demonstrated better postoperative recovery outcomes in single-level lumbar spinal stenosis surgery. Conclusion: The study results support the implementation of ERAS principles in single-level lumbar spinal stenosis surgery to promote rapid recovery, reduce healthcare resource consumption, and improve overall patient satisfaction.展开更多
Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable o...Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable osteoporotic spinal fractures in our hospital were included in this study.They were divided into the conventional group and the observation group based on treatment differences,with 23 patients in each group.The conventional group received conservative drug therapy,while the observation group underwent percutaneous vertebroplasty.The following indicators were compared and analyzed between the two groups:clinical treatment effect and improvement in physical function indicators.Results:The treatment efficiency of the observation group was 95.65%(22/23),while that of the conventional group was 69.57%(16/23).There was a significant difference between the groups,and the treatment effect of the observation group was significantly better(P<0.05).After treatment,the scores of physical status,daily living ability,functional independence,and life obstacles in the observation group were(89.33±4.08),(88.72±4.08),(90.41±2.89),(72.35±3.22),respectively,while those in the conventional group were(68.54±4.21),(67.42±4.11),(73.48±2.75),(72.35±3.22).There was a significant difference between the groups,and the improvement in physical function indicators in the observation group was more pronounced(P<0.05).Conclusion:For patients with old unstable osteoporotic spinal fractures,the basic value of percutaneous vertebroplasty is significant.It can not only improve clinical efficacy and safety but also promote the gradual recovery of patients'physical function indicators.It is recommended for clinical reference and practical application.展开更多
Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human prim...Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.展开更多
In pedicle screw fixation,surgical robot and preoperative planning are enabling technologies to improve the accuracy and safety of pedicle screw placement.In this study,an automatic segmentation method for the pedicle...In pedicle screw fixation,surgical robot and preoperative planning are enabling technologies to improve the accuracy and safety of pedicle screw placement.In this study,an automatic segmentation method for the pedicle and vertebral body is proposed based on the 3D anatomical features of vertebrae.Further,an optimal insertion path is obtained to balance the safety of pedicle screw placement and the vertebral-screw interface strength.The pedicle screw radius is then determined based on the pedicle radius.A classification method is proposed to assess the accuracy of path planning.Finally,the surgical robot’s path can be updated based on the actual positions of the surgical robot and the patient.The CT data of 12 human vertebrae(T6−L5),10 porcine vertebrae(L1−L5)and 5 ovine vertebrae(L1−L5)are used to validate the effectiveness of the proposed method.All pedicle screw placement paths are successfully generated,achieving an excellence or good rate of 98%.Ex vivo pedicle screw placement experiments are conducted on human spine phantom,porcine and ovine spines,and in vivo experiment is conducted on a Bama miniature pig.In the proposed method,both safety and accuracy of pedicle screw placement are improved.According to the widely recognized Gertzbein-Robbins classification,93.18%of the outcomes achieve Grade A,showing promising potential in clinics.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase...Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.展开更多
To enhance the fusion of graft bone in thoracolumbar vertebrae and minimize the postoperative loss of correction, short-segment pedicle screw fixation was reinforced with posterior moselizee bone grafting in vertebrae...To enhance the fusion of graft bone in thoracolumbar vertebrae and minimize the postoperative loss of correction, short-segment pedicle screw fixation was reinforced with posterior moselizee bone grafting in vertebrae for spinal fusion in patients with thoracrolumbar vertebrate fractures. Seventy patients with thoracrolumbar vertebrate fractures were treated by short-segment pedicle screw fixation and were randomly divided into two groups. Fractures in group A （n=20） were rein-forced with posterior morselized bone grafting in vertebrae for spinal fusion, while patients group B （n=50） did not receive the morselized bone grafting for bone fusion. The two groups were compared in terms of kyphotic deformity, anterior vertebral height, instrument failure and neurological functions after the treatment. Frankel grading system was used for the evaluation of neurological evaluation and Denis scoring scale was employed for pain assessment. The results showed that the kyphosis correction was achieved in both group A and group B （group A： 6.4 degree; group B： 5.4 degree）/At the end of follow-up, kyphosis correction was maintained in group A but lost in group B （P=0.0001）. Postoperatively, greater anterior height was achieved in group A than in group B （P〈0.01）. During follow-up study, anterior vertebral height was maintained only in Group A （P〈0.001）. Both group A and group B showed good Denis pain scores （P1 and P2） but group A outdid group B in terms of control of severe and constant pain （P4 and P5）. By Frankel criteria, the changes in neurological functions in group A was better than those of group B （P〈0.001）. It is concluded that reinforcement of short-segment pedicle fixation with morselized bone grafting for the treatment of patients with thoracolumbar vertebrae fracture could achieve and maintain kyphosis correction, and it may also increase and maintain anterior vertebral height. Morselized bone grafting in vertebrae offers immediate spinal stability in patients with thoracolumbar vertebrate fractures, decreases the instrument failure and provides better postoperative pain control than without the morselized bone grafting.展开更多
Recent research based on various animal models has shown the neuroprotective effects of erythropoietin （EPO）. However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients ...Recent research based on various animal models has shown the neuroprotective effects of erythropoietin （EPO）. However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients with spinal cord ischemia-reperfusion （I-R） injury to investigate the clinical application of EPO and methylprednisolone （MP） for the neuroprotection against spinal cord I-R injury. Retrospective analysis of 63 cases of spinal cord I-R injury was performed. The Frankel neurological performance scale was used to evaluate the neurological function after spinal cord injury （SCI）, including 12 cases of scale B, 30 cases of scale C, and 21 cases of scale D. These cases were divided into 2 groups： group A （27 cases） got treatment with both EPO and MP; group B （36 cases） got treatment with MP only. The neurological function of patients after treatment was evaluated by American Spinal Cord Injury Association （ASIA） index score, and activity of daily living （ADL） of the patients was also recorded. All patients got follow-up and the follow-up period ranged from 24 to 39 months （mean 26 months）. There was no significance difference in neurological function between groups A and B before the treatment （P〉0.05）. However, the neurological function and ADL scores were significantly improved 1 week, 1 year or 2 years after the treatment compared to those before the treatment （P〈0.05）, and the improvement was more significant in group A than in group B （P〈0.05）. It is suggested that the clinical application of EPO and MP provides the neuroprotection against spinal cord I-R injury.展开更多
Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new op...Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.展开更多
Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a so...Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.展开更多
Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear.Here, we investigated whether ESCS affects oligodendrocyte...Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear.Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI.ESCS also significantly increased the myelinated area at 28days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 20,30-cyclic-nucleotide 30-phosphodiesterase (CNPase,an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rh BMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI,and rh BMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.展开更多
Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured s...Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured spinal cord remains unknown. The present study established a rat model of acute spinal cord injury by the weight-drop method. Results showed that after injury, the motor behavior ability of rats was reduced and necrotic injury appeared in spinal cord tissues, which was accompanied by increased Nogo-A expression in these tissues. After intravenous injection of high-dose methylprednisolone, although the pathology of spinal cord tissue remained unchanged, Nogo-A expression was reduced, but the level was still higher than normal. These findings implicate that methylprednisolone could inhibit Nogo-A expression, which could be a mechanism by which early high dose methylprednisolone infusion helps preserve spinal cord function after spinal cord injury.展开更多
An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and...An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as wel as injury current, can be modulated by direct current field stimulation;however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV （as the anode-centered group） by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around-70 mV, which is resting membrane potential （as the cathode-centered group） by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon il ustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cel membrane and the reduction of cation influx.展开更多
Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To in...Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.展开更多
文摘Very few reports have described giant pseudomeningoceles ≥ 8 cm in diameter. We report this case of the biggest giant pseudomeningocele at the unusual cervicothoracic level. A 59 year old man who underwent cervicothoracic laminectomy had a giant pseudomeningocele detected and the lesion gradually grew to about 15 cm in diameter by 2 years postoperatively. Cerebrospinal fluid leak closure was performed and the postoperative course was favorable. We present this case, review the literature and discuss the size and portion, mechanism of formation, symptoms and treatments of giant pseudomeningocele.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
文摘BACKGROUND Administering anti-osteoporotic agents to patients perioperatively is a widely accepted approach for improving bone fusion rates and reducing the risk of complications.The best anti-osteoporotic agents for spinal fusion surgery remain unclear.AIM To investigate the efficacy and safety of different anti-osteoporotic agents in spinal fusion surgery via network meta-analysis.METHODS Searches were conducted in four electronic databases(PubMed,EMBASE),Web of Science,the Cochrane Library and China National Knowledge Infrastructure(CNKI)from inception to November 2022.Any studies that compared antiosteoporotic agents vs placebo for spinal fusion surgery were included in this network meta-analysis.Outcomes included fusion rate,Oswestry disability index(ODI),and adverse events.Network meta-analysis was performed by R software with the gemtc package.RESULTS In total,13 randomized controlled trials were included in this network metaanalysis.Only teriparatide(OR 3.2,95%CI:1.4 to 7.8)was more effective than placebo in increasing the fusion rate.The surface under the cumulative ranking curve(SUCRA)of teriparatide combined with denosumab was the highest(SUCRA,90.9%),followed by teriparatide(SUCRA,74.0%),zoledronic acid(SUCRA,43.7%),alendronate(SUCRA,41.1%)and risedronate(SUCRA,35.0%).Teriparatide(MD-15,95%CI:-28 to-2.7)and teriparatide combined with denosumab(MD-20,95%CI:-40 to-0.43)were more effective than placebo in decreasing the ODI.The SUCRA of teriparatide combined with denosumab was highest(SUCRA,90.8%),followed by teriparatide(SUCRA,74.5%),alendronate(SURCA,52.7),risedronate(SURCA,52.1%),zoledronic acid(SURCA,24.2%)and placebo(SURCA,5.6%)for ODI.The adverse events were not different between groups.CONCLUSION This network meta-analysis suggests that teriparatide combined with denosumab and teriparatide alone significantly increase the fusion rate and decrease the ODI without increasing adverse events.Based on current evidence,teriparatide combined with denosumab or teriparatide alone is recommended to increase the fusion rate and to reduce ODI in spinal fusion patients.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
文摘Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained a penetrating cervical spinal cord injury from a sharpened stick.While initially tetraparetic,he rapidly recovered function.The risks of neurological deterioration during surgical removal made the patient reluctant to consent to surgery despite the impalement of the spinal cord.A repeat MRI on day 3 showed an extension of edema indicating progressive inflammation.On the 7~(th)day after injury,fever and paresthesias occurred with a large increase in serum inflammatory indicators,and the patient agreed to undergo surgical removal of the wooden object.We discuss the management nuances related to wood,the longitudinal evolution of MRI findings,infection risk,surgical risk mitigation and technique,an inflammatory marker profile,long-term recovery,and the surprisingly minimal neurological deficits associated with low-velocity midline spinal cord injuries.The patient had an excellent clinical outcome.The main lessons are that a wooden penetrating central nervous system injury has a high risk for infection,and that surgical removal from the spinal cord should be performed soon after injury and under direct visualization.
文摘Objective: With the aging population and changes in lifestyle, lumbar spinal stenosis has become a common spinal disorder. Treatment modalities have been advancing, and the application of Enhanced Recovery After Surgery (ERAS) principles provides a new approach to postoperative recovery in patients. This study aims to investigate the clinical application effects of ERAS principles in single-level lumbar spinal stenosis surgery. Methods: This study included 64 patients who underwent lumbar fusion surgery in the Spinal Surgery Department of Baise People’s Hospital from July 2022 to July 2024. These patients were divided into an experimental group (ERAS group, 33 cases) and a control group (conventional group, 31 cases) based on perioperative care, receiving ERAS principles and traditional treatment, respectively. A comparison was made between the two groups in terms of gender, age, BMI, intraoperative blood loss, postoperative length of hospital stay, postoperative complications, hospital costs, VAS scores (preoperative/postoperative day 3), and ODI scores (preoperative/postoperative day 3). Results: There were no significant differences in gender, age, and BMI between the ERAS group and the conventional group (gender: χ2 = 0.5008, P = 0.4792;age: 54.55 ± 8.51 years vs. 57.39 ± 8.16 years, P = 0.0892;BMI: 25.11 ± 2.70 vs. 24.77 ± 2.75, P = 0.3098). However, during surgery, patients in the ERAS group had significantly less blood loss than those in the conventional group (197.58 ± 195.51ml vs. 438.71 ± 349.22 ml, P = 0.0006), and the postoperative length of hospital stay was significantly shorter (7.00 ± 2.24 days vs. 11.55 ± 5.23 days, P = 0.0000). On postoperative day 3, VAS scores were significantly better in the ERAS group compared to the conventional group (3.70 ± 0.88 vs. 4.32 ± 0.87, P = 0.0031), and the ODI scores showed significant improvement as well (46.00 ± 3.04 vs. 48.00 ± 3.39, P = 0.0078). Although there were no significant differences in postoperative complications and hospital costs (complications: 3 cases vs. 0 cases, P = 0.2154;hospital costs: 63524.29 ± 17891.80 RMB vs. 58733.84 ± 13280.82 RMB, P = 0.1154), ERAS demonstrated better postoperative recovery outcomes in single-level lumbar spinal stenosis surgery. Conclusion: The study results support the implementation of ERAS principles in single-level lumbar spinal stenosis surgery to promote rapid recovery, reduce healthcare resource consumption, and improve overall patient satisfaction.
文摘Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable osteoporotic spinal fractures in our hospital were included in this study.They were divided into the conventional group and the observation group based on treatment differences,with 23 patients in each group.The conventional group received conservative drug therapy,while the observation group underwent percutaneous vertebroplasty.The following indicators were compared and analyzed between the two groups:clinical treatment effect and improvement in physical function indicators.Results:The treatment efficiency of the observation group was 95.65%(22/23),while that of the conventional group was 69.57%(16/23).There was a significant difference between the groups,and the treatment effect of the observation group was significantly better(P<0.05).After treatment,the scores of physical status,daily living ability,functional independence,and life obstacles in the observation group were(89.33±4.08),(88.72±4.08),(90.41±2.89),(72.35±3.22),respectively,while those in the conventional group were(68.54±4.21),(67.42±4.11),(73.48±2.75),(72.35±3.22).There was a significant difference between the groups,and the improvement in physical function indicators in the observation group was more pronounced(P<0.05).Conclusion:For patients with old unstable osteoporotic spinal fractures,the basic value of percutaneous vertebroplasty is significant.It can not only improve clinical efficacy and safety but also promote the gradual recovery of patients'physical function indicators.It is recommended for clinical reference and practical application.
基金supported by the National Natural Science Foundation of China(81972064)the Guangdong Basic and Applied Basic Research Foundation(2021A1515111117,2020A1515011415).
文摘Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
基金Supported by Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515011897)Shenzhen Science and Technology Program(Grant No.KQTD20210811090143060)+1 种基金Sustainable Development Science and Technology Special Project of Shenzhen(Grant No.KCXFZ20230731100900002)Tianjin Municipal Science and Technology Program(Grant No.22JCYBJC01240).
文摘In pedicle screw fixation,surgical robot and preoperative planning are enabling technologies to improve the accuracy and safety of pedicle screw placement.In this study,an automatic segmentation method for the pedicle and vertebral body is proposed based on the 3D anatomical features of vertebrae.Further,an optimal insertion path is obtained to balance the safety of pedicle screw placement and the vertebral-screw interface strength.The pedicle screw radius is then determined based on the pedicle radius.A classification method is proposed to assess the accuracy of path planning.Finally,the surgical robot’s path can be updated based on the actual positions of the surgical robot and the patient.The CT data of 12 human vertebrae(T6−L5),10 porcine vertebrae(L1−L5)and 5 ovine vertebrae(L1−L5)are used to validate the effectiveness of the proposed method.All pedicle screw placement paths are successfully generated,achieving an excellence or good rate of 98%.Ex vivo pedicle screw placement experiments are conducted on human spine phantom,porcine and ovine spines,and in vivo experiment is conducted on a Bama miniature pig.In the proposed method,both safety and accuracy of pedicle screw placement are improved.According to the widely recognized Gertzbein-Robbins classification,93.18%of the outcomes achieve Grade A,showing promising potential in clinics.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported in part by grants from the Young Scientists Awards Foundation of Shandong Province of China,No.BS2013YY049the China Postdoctoral Science Foundation,No.2012M511036
文摘Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
文摘To enhance the fusion of graft bone in thoracolumbar vertebrae and minimize the postoperative loss of correction, short-segment pedicle screw fixation was reinforced with posterior moselizee bone grafting in vertebrae for spinal fusion in patients with thoracrolumbar vertebrate fractures. Seventy patients with thoracrolumbar vertebrate fractures were treated by short-segment pedicle screw fixation and were randomly divided into two groups. Fractures in group A （n=20） were rein-forced with posterior morselized bone grafting in vertebrae for spinal fusion, while patients group B （n=50） did not receive the morselized bone grafting for bone fusion. The two groups were compared in terms of kyphotic deformity, anterior vertebral height, instrument failure and neurological functions after the treatment. Frankel grading system was used for the evaluation of neurological evaluation and Denis scoring scale was employed for pain assessment. The results showed that the kyphosis correction was achieved in both group A and group B （group A： 6.4 degree; group B： 5.4 degree）/At the end of follow-up, kyphosis correction was maintained in group A but lost in group B （P=0.0001）. Postoperatively, greater anterior height was achieved in group A than in group B （P〈0.01）. During follow-up study, anterior vertebral height was maintained only in Group A （P〈0.001）. Both group A and group B showed good Denis pain scores （P1 and P2） but group A outdid group B in terms of control of severe and constant pain （P4 and P5）. By Frankel criteria, the changes in neurological functions in group A was better than those of group B （P〈0.001）. It is concluded that reinforcement of short-segment pedicle fixation with morselized bone grafting for the treatment of patients with thoracolumbar vertebrae fracture could achieve and maintain kyphosis correction, and it may also increase and maintain anterior vertebral height. Morselized bone grafting in vertebrae offers immediate spinal stability in patients with thoracolumbar vertebrate fractures, decreases the instrument failure and provides better postoperative pain control than without the morselized bone grafting.
文摘Recent research based on various animal models has shown the neuroprotective effects of erythropoietin （EPO）. However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients with spinal cord ischemia-reperfusion （I-R） injury to investigate the clinical application of EPO and methylprednisolone （MP） for the neuroprotection against spinal cord I-R injury. Retrospective analysis of 63 cases of spinal cord I-R injury was performed. The Frankel neurological performance scale was used to evaluate the neurological function after spinal cord injury （SCI）, including 12 cases of scale B, 30 cases of scale C, and 21 cases of scale D. These cases were divided into 2 groups： group A （27 cases） got treatment with both EPO and MP; group B （36 cases） got treatment with MP only. The neurological function of patients after treatment was evaluated by American Spinal Cord Injury Association （ASIA） index score, and activity of daily living （ADL） of the patients was also recorded. All patients got follow-up and the follow-up period ranged from 24 to 39 months （mean 26 months）. There was no significance difference in neurological function between groups A and B before the treatment （P〉0.05）. However, the neurological function and ADL scores were significantly improved 1 week, 1 year or 2 years after the treatment compared to those before the treatment （P〈0.05）, and the improvement was more significant in group A than in group B （P〈0.05）. It is suggested that the clinical application of EPO and MP provides the neuroprotection against spinal cord I-R injury.
基金supported by the Natural Science Foundation of Shaanxi Province of China,No.2018JQ8029(to LG)
文摘Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.
基金supported in part by the Ministry of Health,Labour and Welfare Sciences Research Granta Grant-in-Aid for Scientific Research(C)from the Japan Society for the Promotion of Sciencea Grant-in-Aid from the General Insurance Association of Japan
文摘Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.
基金supported by the Natural Science Foundation of Liaoning Province (201602277)the Science and Technology Planning Project of Liaoning Province (LJQ2014091).
文摘Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear.Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI.ESCS also significantly increased the myelinated area at 28days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 20,30-cyclic-nucleotide 30-phosphodiesterase (CNPase,an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rh BMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI,and rh BMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.
文摘Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured spinal cord remains unknown. The present study established a rat model of acute spinal cord injury by the weight-drop method. Results showed that after injury, the motor behavior ability of rats was reduced and necrotic injury appeared in spinal cord tissues, which was accompanied by increased Nogo-A expression in these tissues. After intravenous injection of high-dose methylprednisolone, although the pathology of spinal cord tissue remained unchanged, Nogo-A expression was reduced, but the level was still higher than normal. These findings implicate that methylprednisolone could inhibit Nogo-A expression, which could be a mechanism by which early high dose methylprednisolone infusion helps preserve spinal cord function after spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.51177162
文摘An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as wel as injury current, can be modulated by direct current field stimulation;however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV （as the anode-centered group） by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around-70 mV, which is resting membrane potential （as the cathode-centered group） by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon il ustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cel membrane and the reduction of cation influx.
基金supported by the National Natural Science Foundation of China,Nos. 81771346, 82071383the Natural Science Foundation of Shandong Province (Key Project),No. ZR2020KH007+3 种基金the Taishan Scholar Youth Program of Shandong Province,No. tsqn201812156Academic Promotion Program of Shandong First Medical University,Nos. 2019QL025, 2019RC021Spring Industry Leader Talent Support Plan,No. 201984Rongxiang Regenerative Medicine Fund,No. 2019SDRX-23 (all to BN)。
文摘Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.
