Chinese Association for the Study of Pain:Experts consensus on ultrasound-guided injections for the treatment of spinal pain in China(2020 edition)

Spinal pain(SP)is a common condition that has a major negative impact on a patient’s quality of life.Recent developments in ultrasound-guided injections for the treatment of SP are increasingly being used in clinical practice.This clinical expert consensus describes the purpose,significance,implementation methods,indications,contraindications,and techniques of ultrasound-guided injections.This consensus offers a practical reference point for physicians to implement successfully ultrasound-guided injections in the treatment of chronic SP.

Neurotoxicity of intrathecal injections of dexmedetomidine into the rat spinal dorsal horn

To investigate the neurotoxicity of intrathecal injections of dexmedetomidine,Sprague-Dawley rats were intrathecally injected with dexmedetomidine at doses of 0.75,1.50 and 3.00μg/kg into the spinal dorsal horn.We found that c-Fos expression in the rat spinal dorsal horn peaked at 7 hours following the 3.00μg/kg dexmedetomidine injection,while the levels of c-Fos expression following 0.75 and 1.50μg/kg dexmedetomidine were similar to those in the spinal dorsal horn of normal rats. At 48 hours following administration,the level of c-Fos expression was similar to normal levels.In addition,the intrathecal injections of dexmedetomidine increased paw withdrawal mechanical thresholds and prolonged thermal tail flick latencies.These results indicate that dexmedetomidine has pronounced antinociceptive effects.However,dexmedetomidine appears to have neurotoxic effects in the spinal cord because it increased c-Fos expression in the spinal dorsal horn within 7 hours following administration.

Methylprednisolone intrathecal injections suppress neuronal apoptosis following acute spinal cord injury

High dose methylprednisolone intravenous injections are effective in treating acute spinal cord injury but can have severe side effects. In this study, we investigated intrathecal delivery of methylprednisolone for the treatment of spinal cord injury. In particular, we examined the effects of varying doses of methylprednisolone intrathecal injections on neuronal apoptosis induced by secondary damage. The results demonstrate that intrathecal injections inhibit the expression of interleukin-lβ, significantly lower expression of caspase-3, and reduce the number of apoptotic neurons, High dose methylprednisolone （0.75 mg/μL） was much more effective at reducing neuronal apoptosis than low dose methvlprednisolone （0.01 ma/μL.

Combined Detrusor and External Urethral Sphincter BTX-A Injections for Detrusor Overactivity and Detrusor External Sphincter Dyssynergia Secondary to Spinal Cord Injury

Objective: To evaluate the efficacy and safety of Combined detrusor and external urethral sphincter BTX-A injections for detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. Study Design: Prospective study. Methods: The study was carried out in 18 SCI patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) receiving Combined detrusor and external urethral sphincter BTX-A injections treatment. Contain 200 U botulinum toxin intradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD (PdetmaxDO-DESD), volume at first DO and DESD (VDO-DESD), maximum urethral closure pressure (MUCP), and Incontinence-Specific Quality-of-Life Instrument (I-QoL). Adverse events were recorded. Results: All patients experienced a significant mean reduction in PdetmaxDO-DESD (50.75%), maximum urethral closure pressure (26.34%) and a significant mean increase in VDO-DESD (63.00%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument was also found. No obvious adverse event and toxic effect was observed. Conclusion: Combined detrusor and external urethral sphincter BTX-A injections is a good choice for patients with DO and DESD secondary to spinal cord injury. It could not only protect the upper urinary tract but also improve quality of life.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Passive activity enhances residual control ability in patients with complete spinal cord injury

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.

Steel bar penetrating cervical spinal canal without neurological injury:A case report

BACKGROUND We report a rare case of cervical spinal canal penetrating trauma and review the relevant literatures.CASE SUMMARY A 58-year-old male patient was admitted to the emergency department with a steel bar penetrating the neck,without signs of neurological deficit.Computed tomography(CT)demonstrated that the steel bar had penetrated the cervical spinal canal at the C6–7 level,causing C6 and C7 vertebral body fracture,C6 left lamina fracture,left facet joint fracture,and penetration of the cervical spinal cord.The steel bar was successfully removed through an open surgical procedure by a multidisciplinary team.During the surgery,we found that the cervical vertebra,cervical spinal canal and cervical spinal cord were all severely injured.Postoperative CT demonstrated severe penetration of the cervical spinal canal but the patient returned to a fully functional level without any neurological deficits.CONCLUSION Even with a serious cervical spinal canal penetrating trauma,the patient could resume normal work and life after appropriate treatment.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Surgical Management of Lumbar Spinal Canal Stenosis with Instrumentation at the Yaounde Central Hospital: Comparison of Unilateral versus Bilateral Pedicle Screw Fixation Combined with Transforaminal Lumbar Interbody Fusion

Introduction: The choice of adopting unilateral pedicle screw fixation or using bilateral pedicle screw fixation in lumbar spinal stenosis remains controversial. In our context, very few studies have been performed comparing the clinical effectiveness of unilateral versus bilateral fixation in the surgical management of lumbar spinal canal stenosis. Objective: Evaluate the impact on quality of life and clinical efficacy of unilateral spondylodesis compared to bilateral spondylodesis in the surgical management of lumbar spinal canal stenosis at the Yaounde Central Hospital. Methods: This was a retrospective descriptive cross-sectional study for a period of 4 years, from June 2015 to June 2019. It involved all patients operated for lumbar canal stenosis and who underwent spondylodesis or spinal fusion at the neurosurgery department of the Yaounde Central Hospital. Results: A total of 68 participants were recruited during our study period. 32 (47%) of the study population were in the 50 - 60 age group, with a mean age of 56.98 years ranging from 41 to 75 years. Females, housewives and farmers were the most affected. In our study, 72% of patients had unilateral spondylodesis and 28% had bilateral fusion. Preoperatively, 71% of patients had insurmountable pain, refractory to medical treatment. At 3 months postoperatively, 73.7% of patients with bilateral setup had moderate pain compared to 69% of those with unilateral setup. At 6 months postoperatively, 79% of patients with bilateral fusion had mild pain compared to 82% of patients with unilateral setup. At 1 year postoperatively, all patients had mild pain. Preoperatively, 66.2% of patients were unable to walk and 19.1% of patients were bedridden according to the Oswestry score. At 3 months postoperatively, 10.2% of patients with unilateral setup were unable to walk compared to 10.5% of patients with bilateral fixation, while 67.3% of patients with unilateral fixation had moderate disability compared to 52.6% of patients with bilateral fixation. At 6 months postoperatively, 51% of patients with unilateral setup had moderate disability compared to 47.4% of patients with bilateral fixation, while 42.9% of patients with unilateral fixation had mild disability compared to 42.1% of patients with bilateral fixation. At 1 year postoperatively, 81.6% of patients who underwent unilateral fixation had only mild disability compared to 73.7% of patients with bilateral fixation. Conclusion: The assessment of quality of life according to the set-up used shows similar results at 3 months, 6 months and 1 year, with no statistically significant differences. Single-sided pedicle screw fixation combined with transforaminal lumbar interbody fusion or mounting has the advantage of being faster, with less bleeding and is less expensive compared to bilateral fixation.

Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Clinical Study of Applying Enhanced Recovery after Surgery Concept in Single-Segment Lumbar Spinal Stenosis Surgery

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.

Analgesic Effect of Combined Spinal-Epidural Anesthesia and its Effect on TNF-α and CRP Levels in Elderly Patients with Hip Fracture During Surgical Treatment

Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our hospital from January 2021 to December 2022 were selected and randomly divided into two groups,with 60 cases in the experimental group and 60 in the control group.The experimental group was given combined spinal-epidural anesthesia intervention measures,while the control group was given epidural anesthesia intervention measures.The analgesic effect,tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP)levels,and other observation indicators were analyzed after anesthesia intervention.Result:After the intervention,the analgesic effect and the evaluation results of the subjects in the experimental group were better than those in the control group(P<0.05);the obtained values of TNF-αand CRP levels in the experimental group were higher than those of the control group(P<0.05).Conclusion:The combined spinal-epidural anesthesia intervention demonstrated positive outcomes.The analgesic effect of patients during surgery and their inflammatory factor levels improved,which makes this intervention worthy of clinical application and promotion.

Resident immune responses to spinal cord injury:role of astrocytes and microglia

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.