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...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.展开更多
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 fo...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.展开更多
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 th...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.展开更多
<strong>Objective:</strong> To evaluate the efficacy and safety of Combined detrusor and external urethral sphincter BTX-A injections for detrusor overactivity (DO) and detrusor external sphincter dyssyner...<strong>Objective:</strong> 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. <strong>Study Design:</strong> Prospective study. <strong>Methods:</strong> 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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.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
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...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.展开更多
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 psychoso...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.展开更多
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 s...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.展开更多
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 th...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.展开更多
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 penetr...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.展开更多
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 th...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.展开更多
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 co...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.展开更多
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...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.展开更多
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 i...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.展开更多
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-...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.展开更多
Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the i...Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.展开更多
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hi...Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.展开更多
Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate...Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.展开更多
Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
文摘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.
文摘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.
基金the Research Fund of First Affiliated Hospital,Xinjiang Medical University,China,No.2008-YFY-05the Postgraduate Fund of the First Affiliated Hospital,Xinjiang Medical University,No.2010PGF01
文摘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.
文摘<strong>Objective:</strong> 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. <strong>Study Design:</strong> Prospective study. <strong>Methods:</strong> 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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.
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 grants from the National Health and Medical Research Council(NHMRC)of Australia(Nos.571100 and 1048082)the Baxter Charitable Foundation(to TCL)+1 种基金Medical Research grants from the Rebecca L.Cooper Medical Research Foundation(to MWW,TCL,and MDL)supported by a Charles D.Kelman,M.D.Postdoctoral Award(2010)from the International Retinal Research Foundation(USA)。
文摘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.
文摘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.
基金supported by the Clinical Frontier Technology Program of the First A±liated Hospital of Jinan University,China(No.JNU1AFCFTP-2022-a01212)the Clinical Research Funds for the First Clinical Medicine College of Jinan University(Grant No.2018006).
文摘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.
基金supported by Hong Kong Spinal Cord Injury Fund (HKSCIF),China (to HZ)。
文摘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.
文摘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.
基金supported by the United States Department of Veterans Affairs Rehabilitation Research and Development Service (RR&D)[Merit Review Award numbers B3123-I/101 RX003123 and B3986-R/I01 RX003986-01A1]。
文摘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.
文摘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.
基金Weifang Municipal Science and Technology Bureau(Medical)Project“Effects and Mechanisms of Oxycodone and Alfentanil on IgFs in Mouse Ovarian Granulosa Cells”(2021YX035)。
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.81801226(to QK and XS)and 82101445(to XJ)。
文摘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.
基金supported by the Robert Campeau Family Foundation/Dr.C.H.Tator Chair in Brain and Spinal Cord Research(to MGF)。
文摘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.
基金supported by the National Natural Science Foundation of China,No.81772421(to YH).
文摘Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
基金supported by the Key Projects of the National Natural Science Foundation of China,No.11932013(to XC)Key Military Logistics Research Projects,No.B WJ21J002(to XC)+4 种基金the Key projects of the Special Zone for National Defence Innovation,No.21-163-12-ZT006002-13(to XC)the National Nature Science Foundation of China No.82272255(to XC)the National Defense Science and Technology Outstanding Youth Science Fund Program,No.2021-JCIQ-ZQ-035(to XC)the Scientific Research Innovation Team Project of Armed Police Characteristic Medical Center,No.KYCXTD0104(to ZL)the National Natural Science Foundation of China Youth Fund,No.82004467(to BC)。
文摘Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.
基金funded by grants from the Fondo de Investigacion de la Seguridad Social(Spain)(FIS PI-14/01935)the Spanish Ministerio de Ciencia y Tecnologia+4 种基金Instituto de Salud Carlos III(PI051871,CIBERehd)the Spanish Ministerio de Economia y Competitividad(SAF2017-86343-R)the Comunidad de Madrid(P2022/BMD-7321)HALEKULANY S.L.PROACAPITAL and MJR.
文摘Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.