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
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
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
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
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
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
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
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It a...Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury.The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury.A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra.The rats received an intraperitoneal injection of epothilone B（0.75 mg/kg） at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group.Neuron-glial antigen 2,platelet-derived growth factor receptor β,and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group,but β-tubulin protein expression was greater.Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment.The Basso,Beattie,and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group.The results of this study demonstrated that epothilone B reduced the number of pericytes,inhibited extracellular matrix formation,and suppressed scar formation after spinal cord injury.展开更多
Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understo...Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understood.In this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control group.We found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control group.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle contraction.We also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this pathway.These results indicate successful detection of some important proteins that play potential roles in spinal cord injury.Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014.展开更多
BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it...BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury. OBJECTIVE： Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells （OECs）, irradiated by LPL, on functional repair of rats following transversal spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008. MATERIALS： A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture. The remaining 40 rats were used to establish T12 complete spinal cord transection injury. DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon, USA, and the LY/JG650-D500-16 low-power laser was produced by Xi＇an Lingyue Electromechanical Science And Technology Co., Ltd., China. METHODS： The successful rat models were randomly divided into three groups： OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium （10μL） respectively 4 weeks after spinal cord was completely transected at the T12 level. MAIN OUTCOME MEASURES： Spinal cord injury was observed using hematoxylin-eosin staining Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan （BBB） scores were used to evaluate motor functions of rat lower limbs. RESULTS： Structural disturbances were observed following spinal cord injury in each group, and a large amount of scar tissue covered the broken ends, accompanied by porosis and inflammatory cell infiltration. Following OEC transplantation, the distal end connected to the proximal end. nerve growth factor receptor p75 and glial fibrillary acidic protein immunohistochemistry revealed positive OECs in the cephalad and caudal area of rats that received LPL-irradiated OEC transplantation. In the OECs group, only glial fibrillary acidic protein staining was observed. No staining was found in the control group. Neural fibers labeled with Fluorogold extended across the lesion area and into the cephalad and caudal area in the OECs and LPL-irradiated OECs groups, but were not present in the control group. BBB scores revealed statistically significant differences among the three groups （P 〈 0.05）： OECs irradiated by LPL group 〉 OECs group 〉 control group. CONCLUSION： Transplantation of OECs and LPL-irradiated OECs promoted functional repair in the injured spinal cord of rats, although LPL-irradiated OECs resulted in greater beneficial effects.展开更多
To investigate characteristics of injury potentials after different degrees of spinal cord injury in rats the present study established models of spinal cord contusion with severe, moderate, and mild degrees of injury...To investigate characteristics of injury potentials after different degrees of spinal cord injury in rats the present study established models of spinal cord contusion with severe, moderate, and mild degrees of injury. Injury potential was measured in vivo using a direct current voltage amplification system. Results revealed that in the first 4 hours after acute spinal cord injury, initial amplitude of injury potential was greatest after severe injury, followed by moderate and mild injuries. Amplitude of injury potential decreased gradually with injury time, and the recession curve was logarithmic. Under the same degree of injuries, amplitude of rostral injury potential was generally less than caudal injury potential. Results suggested that injury potential reflected injury severity, because large initial amplitude of injury potential during the early injury stage implied severe injury.展开更多
BACKGROUND： lnterleukin-2 （IL-2） may influence the growth and survival of nerve cells following spinal cord injury and resuscitate the proliferation and maturation of oligodendrocytes. OBJECTIVE： To observe the ef...BACKGROUND： lnterleukin-2 （IL-2） may influence the growth and survival of nerve cells following spinal cord injury and resuscitate the proliferation and maturation of oligodendrocytes. OBJECTIVE： To observe the effect of IL-2 on neuronal apoptosis of neurogliocytes at different times following acute spinal cord injury in rats. DESIGN, TIME AND SETTING： A randomized grouping trial based on cellular morphology was performed at the Institute of Traumatic Orthopedics of Shandong Province between October 2004 and January 2006. MATERIALS： A total of 72 adult, male, Sprague Dawley rats were included in this study and were divided into a control group and an IL-2 group. The Bcl-2 monoclonal antibody and TUNEL kit were purchased from Wunan Boster Biological Technology Corporation. METHODS： Spinal cord injury was induced in all the rats by dropping a weight from a height of 25 cm onto the exposed spinal cord at vertebral levels T7-11, thus producing a mild lesion. Immediately following the modeling, the rats were injected with daily IL-2 （10 uL） intramuscularly （the IL-2 group）. Other rats received an injection of physiological saline 0.5 mL/d （the control group）. MAIN OUTCOME MEASURES： Bcl-2 immunohistochemistry was applied to detect the Bcl-protein and positive cell expression. The TUNEL method was used to count the number of apoptotic cells. RESULTS： The expression level of Bcl-2 proteins increased significantly in spinal cord tissues during the first day after acute spinal cord injury, reaching a peak on days 3 and days 8 in the control and IL-2 groups, respectively. They were more prevalent in neurogliocytes than in neurocytes, and then began to decrease on day 14. From then until day 21, less expression was detected （P 〈 0.05）. In the control group, many apoptotic cells existed after 24 hours, and most of them were gliocytes; apoptotic cells reached a peak after 3-8 days. They then decreased gradually until day 21, when a small number of cells were still available. In the IL-2 group, the number of positive cells was significantly lower than in the control group （P 〈 0.05）. CONCLUSION： The expression of Bcl-2 and the number of apoptotic cells in neurogliocytes undergo similar changes with time after acute spinal cord injury. IL-2 may upregulate the expression of Bcl-2 proteins and decrease cell apoptosis in spinal cord tissue.展开更多
We have previously shown that induction of ketosis by ketogenic diet(KD)conveyed neuroprotection following spinal cord injury in rodent models,however,clinical translation may be limited by the slow raise of ketone le...We have previously shown that induction of ketosis by ketogenic diet(KD)conveyed neuroprotection following spinal cord injury in rodent models,however,clinical translation may be limited by the slow raise of ketone levels when applying KD in the acute post-injury period.Thus we investigated the use of exogenous ketone supplementation(ketone sodium,KS)combined with ketogenic diet as a means rapidly inducing a metabolic state of ketosis following spinal cord injury in adult rats.In uninjured rats,ketone levels increased more rapidly than those in rats with KD alone and peaked at higher levels than we previously demonstrated for the KD in models of spinal cord injury.However,ketone levels in KD+KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD alone.We still demonstrated neuroprotective effects of KD+KS treatment that extend our previous neuroprotective observations with KD only.The results showed increased neuronal and axonal sparing in the dorsal corticospinal tract.Also,better performance of forelimb motor abilities were observed on the Montoya staircase(for testing food pellets reaching)at 4 and 6 weeks post-injury and rearing in a cylinder(for testing forelimb usage)at 6 and 8 weeks post-injury.Taken together,the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following neurotrauma.Ketone salt combined with a ketogenic diet gavage in rats with acute spinal cord injury can rapidly increase ketone body levels in the blood and promote motor function recovery.This study was approved by the Animal Care Committee of the University of British Columbia(protocol No.A14-350)on August 31,2015.展开更多
BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a stro...BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus,the pathogenesis of SCI is still under investigation.AIM To determine the key genes based on the modularization of in-depth analysis,in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI.METHODS Firstly,the differences between injured and non-injured spinal cord of astrocyte(HA),injured and non-injured spinal cord of non-astrocyte(FLOW),injured spinal cord of non-injured astrocyte(HA)and non-injured spinal cord of nonastrocyte(FLOW),and non-injured spinal cord of astrocyte(HA)and nonastrocyte(FLOW)were analyzed.The total number of differentially expressed genes was obtained by merging the four groups of differential results.Secondly,the genes were co-expressed and clustered.Then,the enrichment of GO function and KEGG pathway of module genes was analyzed.Finally,non-coding RNA,transcription factors and drugs that regulate module genes were predicted using hypergeometric tests.RESULTS In summary,we obtained 19 expression modules involving 5216 differentially expressed genes.Among them,miR-494,XIST and other genes were differentially expressed in SCI patients,and played an active regulatory role in dysfunction module,and these genes were recognized as the driving genes of SCI.Enrichment results showed that module genes were significantly involved in the biological processes of inflammation,oxidation and apoptosis.Signal pathways such as NF-kappa B/A20,AMPK and MAPK were significantly regulated.In addition,non-coding RNA pivot(including miR-136-5p and let-7d-5p,etc.)and transcription factor pivot(including NFKB1,MYC,etc.)were identified as significant regulatory dysfunction modules.CONCLUSION Overall,this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI.These findings helped to reveal the core dysfunction modules,potential regulatory factors and driving genes of the disease,and to improve our understanding of its pathogenesis.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
A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and po...A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and polymerase chain reaction enzyme-linked immunosorbent assay results demonstrated that glial fibrillary acidic protein and telomerase expression increased gradually after injury, peaked at 28 days, and then gradually decreased. Spearman rank correlation showed a positive correlation between glial fibrillary acidic protein expression and telomerase expression in the glial scar. These results suggest that telomerase promotes glial scar formation.展开更多
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
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.
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.
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.
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.
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 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.
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 by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
基金supported by a grant from the Science and Technology Developing Program of Shandong Provincial Government of China,No.2010GSF10254a grant from the Medical and Health Science and Technology Plan Project of Shandong Province of China,No.2015WS0504
文摘Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury.The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury.A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra.The rats received an intraperitoneal injection of epothilone B（0.75 mg/kg） at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group.Neuron-glial antigen 2,platelet-derived growth factor receptor β,and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group,but β-tubulin protein expression was greater.Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment.The Basso,Beattie,and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group.The results of this study demonstrated that epothilone B reduced the number of pericytes,inhibited extracellular matrix formation,and suppressed scar formation after spinal cord injury.
文摘Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understood.In this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control group.We found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control group.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle contraction.We also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this pathway.These results indicate successful detection of some important proteins that play potential roles in spinal cord injury.Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014.
基金Supported by:Scientific Research Program of the Higher Education Institution of Xinjiang,No. XJEDU2006133
文摘BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury. OBJECTIVE： Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells （OECs）, irradiated by LPL, on functional repair of rats following transversal spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008. MATERIALS： A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture. The remaining 40 rats were used to establish T12 complete spinal cord transection injury. DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon, USA, and the LY/JG650-D500-16 low-power laser was produced by Xi＇an Lingyue Electromechanical Science And Technology Co., Ltd., China. METHODS： The successful rat models were randomly divided into three groups： OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium （10μL） respectively 4 weeks after spinal cord was completely transected at the T12 level. MAIN OUTCOME MEASURES： Spinal cord injury was observed using hematoxylin-eosin staining Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan （BBB） scores were used to evaluate motor functions of rat lower limbs. RESULTS： Structural disturbances were observed following spinal cord injury in each group, and a large amount of scar tissue covered the broken ends, accompanied by porosis and inflammatory cell infiltration. Following OEC transplantation, the distal end connected to the proximal end. nerve growth factor receptor p75 and glial fibrillary acidic protein immunohistochemistry revealed positive OECs in the cephalad and caudal area of rats that received LPL-irradiated OEC transplantation. In the OECs group, only glial fibrillary acidic protein staining was observed. No staining was found in the control group. Neural fibers labeled with Fluorogold extended across the lesion area and into the cephalad and caudal area in the OECs and LPL-irradiated OECs groups, but were not present in the control group. BBB scores revealed statistically significant differences among the three groups （P 〈 0.05）： OECs irradiated by LPL group 〉 OECs group 〉 control group. CONCLUSION： Transplantation of OECs and LPL-irradiated OECs promoted functional repair in the injured spinal cord of rats, although LPL-irradiated OECs resulted in greater beneficial effects.
基金Science & Technology Program of Chinese Academy of Sciences for Disability,No.KGLX2-YW-613the New Star Program of Beijing Science and Technology,No.2007B070
文摘To investigate characteristics of injury potentials after different degrees of spinal cord injury in rats the present study established models of spinal cord contusion with severe, moderate, and mild degrees of injury. Injury potential was measured in vivo using a direct current voltage amplification system. Results revealed that in the first 4 hours after acute spinal cord injury, initial amplitude of injury potential was greatest after severe injury, followed by moderate and mild injuries. Amplitude of injury potential decreased gradually with injury time, and the recession curve was logarithmic. Under the same degree of injuries, amplitude of rostral injury potential was generally less than caudal injury potential. Results suggested that injury potential reflected injury severity, because large initial amplitude of injury potential during the early injury stage implied severe injury.
文摘BACKGROUND： lnterleukin-2 （IL-2） may influence the growth and survival of nerve cells following spinal cord injury and resuscitate the proliferation and maturation of oligodendrocytes. OBJECTIVE： To observe the effect of IL-2 on neuronal apoptosis of neurogliocytes at different times following acute spinal cord injury in rats. DESIGN, TIME AND SETTING： A randomized grouping trial based on cellular morphology was performed at the Institute of Traumatic Orthopedics of Shandong Province between October 2004 and January 2006. MATERIALS： A total of 72 adult, male, Sprague Dawley rats were included in this study and were divided into a control group and an IL-2 group. The Bcl-2 monoclonal antibody and TUNEL kit were purchased from Wunan Boster Biological Technology Corporation. METHODS： Spinal cord injury was induced in all the rats by dropping a weight from a height of 25 cm onto the exposed spinal cord at vertebral levels T7-11, thus producing a mild lesion. Immediately following the modeling, the rats were injected with daily IL-2 （10 uL） intramuscularly （the IL-2 group）. Other rats received an injection of physiological saline 0.5 mL/d （the control group）. MAIN OUTCOME MEASURES： Bcl-2 immunohistochemistry was applied to detect the Bcl-protein and positive cell expression. The TUNEL method was used to count the number of apoptotic cells. RESULTS： The expression level of Bcl-2 proteins increased significantly in spinal cord tissues during the first day after acute spinal cord injury, reaching a peak on days 3 and days 8 in the control and IL-2 groups, respectively. They were more prevalent in neurogliocytes than in neurocytes, and then began to decrease on day 14. From then until day 21, less expression was detected （P 〈 0.05）. In the control group, many apoptotic cells existed after 24 hours, and most of them were gliocytes; apoptotic cells reached a peak after 3-8 days. They then decreased gradually until day 21, when a small number of cells were still available. In the IL-2 group, the number of positive cells was significantly lower than in the control group （P 〈 0.05）. CONCLUSION： The expression of Bcl-2 and the number of apoptotic cells in neurogliocytes undergo similar changes with time after acute spinal cord injury. IL-2 may upregulate the expression of Bcl-2 proteins and decrease cell apoptosis in spinal cord tissue.
基金supported by the Craig Neilsen Foundation(to WT)the Canadian Institutes for Health Research(to WT)+2 种基金supported by the China Scholarship Council(No.201508500102)a visiting trainee stipend from the Blusson Integrated Cure Partnershipthe John and Penny Ryan British Columbia Leadership Chair in Spinal Cord Research funded in part by the Rick Hansen Foundation
文摘We have previously shown that induction of ketosis by ketogenic diet(KD)conveyed neuroprotection following spinal cord injury in rodent models,however,clinical translation may be limited by the slow raise of ketone levels when applying KD in the acute post-injury period.Thus we investigated the use of exogenous ketone supplementation(ketone sodium,KS)combined with ketogenic diet as a means rapidly inducing a metabolic state of ketosis following spinal cord injury in adult rats.In uninjured rats,ketone levels increased more rapidly than those in rats with KD alone and peaked at higher levels than we previously demonstrated for the KD in models of spinal cord injury.However,ketone levels in KD+KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD alone.We still demonstrated neuroprotective effects of KD+KS treatment that extend our previous neuroprotective observations with KD only.The results showed increased neuronal and axonal sparing in the dorsal corticospinal tract.Also,better performance of forelimb motor abilities were observed on the Montoya staircase(for testing food pellets reaching)at 4 and 6 weeks post-injury and rearing in a cylinder(for testing forelimb usage)at 6 and 8 weeks post-injury.Taken together,the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following neurotrauma.Ketone salt combined with a ketogenic diet gavage in rats with acute spinal cord injury can rapidly increase ketone body levels in the blood and promote motor function recovery.This study was approved by the Animal Care Committee of the University of British Columbia(protocol No.A14-350)on August 31,2015.
文摘BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus,the pathogenesis of SCI is still under investigation.AIM To determine the key genes based on the modularization of in-depth analysis,in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI.METHODS Firstly,the differences between injured and non-injured spinal cord of astrocyte(HA),injured and non-injured spinal cord of non-astrocyte(FLOW),injured spinal cord of non-injured astrocyte(HA)and non-injured spinal cord of nonastrocyte(FLOW),and non-injured spinal cord of astrocyte(HA)and nonastrocyte(FLOW)were analyzed.The total number of differentially expressed genes was obtained by merging the four groups of differential results.Secondly,the genes were co-expressed and clustered.Then,the enrichment of GO function and KEGG pathway of module genes was analyzed.Finally,non-coding RNA,transcription factors and drugs that regulate module genes were predicted using hypergeometric tests.RESULTS In summary,we obtained 19 expression modules involving 5216 differentially expressed genes.Among them,miR-494,XIST and other genes were differentially expressed in SCI patients,and played an active regulatory role in dysfunction module,and these genes were recognized as the driving genes of SCI.Enrichment results showed that module genes were significantly involved in the biological processes of inflammation,oxidation and apoptosis.Signal pathways such as NF-kappa B/A20,AMPK and MAPK were significantly regulated.In addition,non-coding RNA pivot(including miR-136-5p and let-7d-5p,etc.)and transcription factor pivot(including NFKB1,MYC,etc.)were identified as significant regulatory dysfunction modules.CONCLUSION Overall,this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI.These findings helped to reveal the core dysfunction modules,potential regulatory factors and driving genes of the disease,and to improve our understanding of its pathogenesis.
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.
基金funded by the National Natural Science Foundation of China, No. 81060106
文摘A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and polymerase chain reaction enzyme-linked immunosorbent assay results demonstrated that glial fibrillary acidic protein and telomerase expression increased gradually after injury, peaked at 28 days, and then gradually decreased. Spearman rank correlation showed a positive correlation between glial fibrillary acidic protein expression and telomerase expression in the glial scar. These results suggest that telomerase promotes glial scar formation.
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.
