Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain,although the mechanisms by which it occurs and leads to pain remain unclear.In healthy adult discs,vessels and nerves are presen...Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain,although the mechanisms by which it occurs and leads to pain remain unclear.In healthy adult discs,vessels and nerves are present only in the outer layer of the annulus fibrosus and in the bony endplate.Animal models,and histological and biomechanical studies have shown that annulus tear or endplate injury is the initiating factor for painful disc degeneration.Injury to the disc triggers a local inflammatory repair response that activates nociceptors and promotes the synthesis of neuropeptides such as substance P and calcitonin generelated peptide,by dorsal root ganglion neurons.These neuropeptides are transported to injured discs and act as pro-inflammatory molecules,promoting the production of an“inflammatory soup”by inducing vasodilatation and plasma extravasation as well as by promoting the release of chemical mediators from disc cells and infiltrating immune cells,causing neurogenic inflammation that leads to progressive disc degeneration and discogenic pain.展开更多
Objectives:This study employed evidence mapping to systematically evaluate clinical practice guidelines(CPGs)for neurogenic bladder(NB)care.We aimed to identify research trends,evidence gaps,and consensus patterns to ...Objectives:This study employed evidence mapping to systematically evaluate clinical practice guidelines(CPGs)for neurogenic bladder(NB)care.We aimed to identify research trends,evidence gaps,and consensus patterns to inform evidence-based nursing practices and support the formulation of highquality CPGs.Methods:A systematic search of electronic databases and guideline repositories was conducted,included PubMed,Web of Science,Embase,Guidelines International Network(GIN),ect.Eligible NB guidelines underwent dual-researcher screening and extraction,and methodological and recommendation quality were assessed using the Appraisal of Guidelines for Research and Evaluation II(AGREE II)and Evaluation-Recommendations Excellence(AGREE-REX)instruments.Five researchers independently evaluated recommendation specificity,evidence grading systems,and implementation consistency.Discrepancies were resolved through consensus discussion or third-party arbitration.Results:Analysis of 19 CPGs(2006–2023)from 11 countries/regions revealed that 78.95%(15/19)incorporated evidence grading systems and 68.42%(13/19)specifiedrecommendation strength.The AGREE II evaluation identifiedcritical methodological deficiencies,with three domains scoring below the acceptable thresholds:Rigor of Development(41.70%),Editorial Independence(43.30%),and Applicability(30.00%).The AGREE-REX results showed moderate performance in Clinical Applicability(55.56%)and implantability(41.67%)but severe gaps in Values and Preferences(25.00%).A systematic synthesis identified40 recommendations:90%(36/40)demonstrated consensus and 10%(4/40)contradictions.These studies addressed the following six clinical themes:1)nursing assessment,2)manipulation-assisted voiding,3)behavioral therapy,4)intermittent catheterization,5)indwelling catheterization,and 6)other therapies.Conclusions:The methodologies and recommendations of the CPGs for NB in nursing demonstrated substantial variability.Therefore,there is an urgent need to improve the quality of the NB-related CPGs.More in-depth research and timely updates are required to enhance the practical utility of CPGs and narrow the gap between CPGs and clinical practice.展开更多
In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports t...In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration.Recently,non-neuronal cells,including IVD cells and infiltrating immune cells,have emerged as important players in neurogenic inflammation.IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system.In return,IVD cells and immune cells produce neuropeptides and nerve growth factor,which stimulate nerve fibers.This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD.Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs.These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs.Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.展开更多
Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying ...Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.展开更多
Adult neurogenesis is a highly dynamic process that leads to the production of new neurons from a population of quiescent neural stem cells(NSCs).In response to specific endogenous and/or external stimuli,NSCs enter a...Adult neurogenesis is a highly dynamic process that leads to the production of new neurons from a population of quiescent neural stem cells(NSCs).In response to specific endogenous and/or external stimuli,NSCs enter a state of mitotic activation,initiating proliferation and differentiation pathways.Throughout this process,NSCs give rise to neural progenitors,which undergo multiple replicative and differentiative steps,each governed by precise molecular pathways that coordinate cellular changes and signals from the surrounding neurogenic niche.展开更多
Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bla...Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bladder capacity,storage,and voiding functions through simple,realistic,and resource-friendly approaches.It involves a structured series of steps,from history-taking and physical examination to bladder-emptying procedures,monitoring urine leaks,assessing reflex voiding,measuring post-void residual(PVR),and calculating total bladder capacity.These evaluations help differentiate between upper motor neuron and lower motor neuron bladder dysfunction,providing critical insights for tailored management.The interpretation of findings focuses on identifying bladder type,assessing leak timing and volume,evaluating reflex voiding,and measuring PVR and total bladder capacity.The results guide interventions such as timing selfclean intermittent catheterization,adjusting fluid intake,and using bladder diaries to monitor patterns.Clinical bladder evaluation is particularly advantageous in low-resource settings,as it avoids the risks and costs associated with urodynamic studies while reflecting real-life patient conditions more effectively.Despite its benefits,no validation studies currently exist for clinical bladder assessment,and its parameters,like maximum voided volume,remain underexplored compared to urodynamic measures.Given the accessibility,affordability,and practicality of this approach,it holds promise for widespread application,especially in primary care settings and among economically disadvantaged populations.This editorial describes the process step-by-step and highlights its role in improving patient outcomes while minimizing complications.展开更多
The purpose of this study was to explore the application of TCM-appropriate technology in neurogenic bladder rehabilitation nursing.Firstly,the background and contents of the study were introduced.Then,it summarizes t...The purpose of this study was to explore the application of TCM-appropriate technology in neurogenic bladder rehabilitation nursing.Firstly,the background and contents of the study were introduced.Then,it summarizes the definition and development of TCM-appropriate technology and expounds the main therapy and application of TCM-appropriate technology in the rehabilitation nursing field.Besides,the pathophysiological characteristics,rehabilitation nursing measures,and rehabilitation difficulties of the neurogenic bladder are described.Then,the application method,effect and prospect of TCM-suitable technology in rehabilitation nursing of neurogenic bladder are described.In addition,the object,method,result analysis,and conclusion of the experimental study are introduced,the main results of this study are summarized,and the future research direction is prospected.In summary,this study aims to provide effective TCM-appropriate technology for neurogenic bladder rehabilitation nursing and provide a reference for clinical practice and theoretical research in related fields.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neur...Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.展开更多
Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-deri...Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
Neurogenic bladder (NB) mainly occurs in patients with spinal cord injury (SCI). The pathological basis of NB is the occurrence of lesions in the urination control center, which requires systematic treatment. Western ...Neurogenic bladder (NB) mainly occurs in patients with spinal cord injury (SCI). The pathological basis of NB is the occurrence of lesions in the urination control center, which requires systematic treatment. Western medicine has many treatment methods for this disease, which can alleviate the symptoms of the disease. However, the radical effect is not ideal and there are many adverse reactions. In comparison, acupuncture can improve the residual urine volume of NB patients and regulate the related indexes of urodynamics. There are many kinds of acupuncture therapies, such as simple acupuncture and moxibustion, which can comprehensively improve the therapeutic effect and obtain a better disease prognosis. Therefore, this article elaborates on the pathogenesis of SCI complicated with NB, the treatment mechanism, and treatment methods of acupuncture and moxibustion to provide a reference for clinical treatment.展开更多
Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor defic...Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.展开更多
Objective:To elucidate the underlying mechanism and effect of electroacupuncture(EA)on the neurogenic bladder following suprasacral spinal cord injury(ssCI).A rat model of detrusor hyperreflexia after SsCI was establi...Objective:To elucidate the underlying mechanism and effect of electroacupuncture(EA)on the neurogenic bladder following suprasacral spinal cord injury(ssCI).A rat model of detrusor hyperreflexia after SsCI was established to examine the urodynamics,detrusor muscle tissue morphology,the protein and mRNA expression levels of pituitary adenylate cyclase activating peptide(PACAP)and its receptor PAC1R,and cyclic adenosine monophosphate(cAMP)content in the detrusor muscle with a focus on the PACAPcAMP signaling pathway.Method:A total of 72 female SD rats were randomized into control group and sham operation group(n=12 per group)by using a random number table.The remaining 48 rats were established into the model of detrusor hyperreflexia after SsCI.After successful modeling,these rats were randomly assigned to model,EA,and EA+PACAP6-38 groups(n=12 per group).The unsuccessful modeled rats were used for exploratory observation.For the rats in EA group,"Ciliao(BL32)""Zhongji(CV3)",and"Sanyinjiao(SP6)"were needled and stimulated by EA.The PACAP receptor antagonist PACAP6-38 was administered intraperitoneally in the EA+PACAP6-38 group before EA,and EA was applied for seven consecutive days.After treatment,the urodynamics of the rats were analyzed,and hematoxylin and eosin staining was used to examine rat bladder detrusor tissue morphology.The expressions of PACAP-38 and PAC1R were detected by immunohistochemistry and Western blot.The mRNA expression levels of PACAP-38 and PAC1R were examined by RT-qPCR,while cAMP content was detected by ELISA.Results:(1)Compared with sham operation group,it was exhibited disarray in the transitional epithelium cells of the bladder in the modeled rats.The intercellular space was significantly widened,accompanied by inflammatory cell infiltration and noticeable tissue edema.Both the bladder initial pressure and leak point pressure of the rats were higher(P<0.01),whereas the maximum cystometric capacity and bladder compliance were lower(P<0.01).The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle,together with the cAMP content,were lower(P<0.05).(2)Compared with the model rats,the EA group showed reduced inflammatory response in the detrusor muscle tissue,with decreased monocyte infiltration and less severe tissue edema.The bladder smooth muscle cells exhibited increased integrity,and there was decreased cellular tissue edema,inflammatory cell infiltration,and fibroplasia.The bladder initial pressure and leak point pressure were lower(P<0.05),while the maximum cystometric capacity and bladder compliance were higher(P<0.01).The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle,along with the cAMP content,were higher(P<0.05).(3)Compared to the EA group,the EA+PACAP6-38 group showed a less organized arrangement of muscle fibers in the detrusor muscle tissue,larger intercellular space,monocyte infltration,and considerable tissue edema.The changes in bladder initial pressure and leak point pressure were not significant(P>0.05),while the maximum cystometric capacity and bladder compliance were lower(P<0.05).The changes in the protein and mRNA expressions of PACAP-38 within the detrusor muscle were not signifcant(P>0.05),whereas the protein and mRNA expressions of PAC1R were reduced(P<0.05),and the cAMP content within the detrusor muscle was lower(P<0.05).Conclusion:EA can ameliorate the uninhibited contractile condition of the detrusor muscle in the bladder following SSCI.By mediating the PACAP-cAMP signaling pathway,it reduces the pathological damage to the detrusor muscle,thereby improving bladder function.展开更多
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tra...Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.展开更多
Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficie...Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflam- matory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.展开更多
文摘Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain,although the mechanisms by which it occurs and leads to pain remain unclear.In healthy adult discs,vessels and nerves are present only in the outer layer of the annulus fibrosus and in the bony endplate.Animal models,and histological and biomechanical studies have shown that annulus tear or endplate injury is the initiating factor for painful disc degeneration.Injury to the disc triggers a local inflammatory repair response that activates nociceptors and promotes the synthesis of neuropeptides such as substance P and calcitonin generelated peptide,by dorsal root ganglion neurons.These neuropeptides are transported to injured discs and act as pro-inflammatory molecules,promoting the production of an“inflammatory soup”by inducing vasodilatation and plasma extravasation as well as by promoting the release of chemical mediators from disc cells and infiltrating immune cells,causing neurogenic inflammation that leads to progressive disc degeneration and discogenic pain.
文摘Objectives:This study employed evidence mapping to systematically evaluate clinical practice guidelines(CPGs)for neurogenic bladder(NB)care.We aimed to identify research trends,evidence gaps,and consensus patterns to inform evidence-based nursing practices and support the formulation of highquality CPGs.Methods:A systematic search of electronic databases and guideline repositories was conducted,included PubMed,Web of Science,Embase,Guidelines International Network(GIN),ect.Eligible NB guidelines underwent dual-researcher screening and extraction,and methodological and recommendation quality were assessed using the Appraisal of Guidelines for Research and Evaluation II(AGREE II)and Evaluation-Recommendations Excellence(AGREE-REX)instruments.Five researchers independently evaluated recommendation specificity,evidence grading systems,and implementation consistency.Discrepancies were resolved through consensus discussion or third-party arbitration.Results:Analysis of 19 CPGs(2006–2023)from 11 countries/regions revealed that 78.95%(15/19)incorporated evidence grading systems and 68.42%(13/19)specifiedrecommendation strength.The AGREE II evaluation identifiedcritical methodological deficiencies,with three domains scoring below the acceptable thresholds:Rigor of Development(41.70%),Editorial Independence(43.30%),and Applicability(30.00%).The AGREE-REX results showed moderate performance in Clinical Applicability(55.56%)and implantability(41.67%)but severe gaps in Values and Preferences(25.00%).A systematic synthesis identified40 recommendations:90%(36/40)demonstrated consensus and 10%(4/40)contradictions.These studies addressed the following six clinical themes:1)nursing assessment,2)manipulation-assisted voiding,3)behavioral therapy,4)intermittent catheterization,5)indwelling catheterization,and 6)other therapies.Conclusions:The methodologies and recommendations of the CPGs for NB in nursing demonstrated substantial variability.Therefore,there is an urgent need to improve the quality of the NB-related CPGs.More in-depth research and timely updates are required to enhance the practical utility of CPGs and narrow the gap between CPGs and clinical practice.
文摘In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration.Recently,non-neuronal cells,including IVD cells and infiltrating immune cells,have emerged as important players in neurogenic inflammation.IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system.In return,IVD cells and immune cells produce neuropeptides and nerve growth factor,which stimulate nerve fibers.This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD.Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs.These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs.Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.
基金supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science KAKENHI 22K09110.
文摘Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.
文摘Adult neurogenesis is a highly dynamic process that leads to the production of new neurons from a population of quiescent neural stem cells(NSCs).In response to specific endogenous and/or external stimuli,NSCs enter a state of mitotic activation,initiating proliferation and differentiation pathways.Throughout this process,NSCs give rise to neural progenitors,which undergo multiple replicative and differentiative steps,each governed by precise molecular pathways that coordinate cellular changes and signals from the surrounding neurogenic niche.
文摘Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bladder capacity,storage,and voiding functions through simple,realistic,and resource-friendly approaches.It involves a structured series of steps,from history-taking and physical examination to bladder-emptying procedures,monitoring urine leaks,assessing reflex voiding,measuring post-void residual(PVR),and calculating total bladder capacity.These evaluations help differentiate between upper motor neuron and lower motor neuron bladder dysfunction,providing critical insights for tailored management.The interpretation of findings focuses on identifying bladder type,assessing leak timing and volume,evaluating reflex voiding,and measuring PVR and total bladder capacity.The results guide interventions such as timing selfclean intermittent catheterization,adjusting fluid intake,and using bladder diaries to monitor patterns.Clinical bladder evaluation is particularly advantageous in low-resource settings,as it avoids the risks and costs associated with urodynamic studies while reflecting real-life patient conditions more effectively.Despite its benefits,no validation studies currently exist for clinical bladder assessment,and its parameters,like maximum voided volume,remain underexplored compared to urodynamic measures.Given the accessibility,affordability,and practicality of this approach,it holds promise for widespread application,especially in primary care settings and among economically disadvantaged populations.This editorial describes the process step-by-step and highlights its role in improving patient outcomes while minimizing complications.
文摘The purpose of this study was to explore the application of TCM-appropriate technology in neurogenic bladder rehabilitation nursing.Firstly,the background and contents of the study were introduced.Then,it summarizes the definition and development of TCM-appropriate technology and expounds the main therapy and application of TCM-appropriate technology in the rehabilitation nursing field.Besides,the pathophysiological characteristics,rehabilitation nursing measures,and rehabilitation difficulties of the neurogenic bladder are described.Then,the application method,effect and prospect of TCM-suitable technology in rehabilitation nursing of neurogenic bladder are described.In addition,the object,method,result analysis,and conclusion of the experimental study are introduced,the main results of this study are summarized,and the future research direction is prospected.In summary,this study aims to provide effective TCM-appropriate technology for neurogenic bladder rehabilitation nursing and provide a reference for clinical practice and theoretical research in related fields.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by the SIAT Innovation Program for Excellent Young Researchers,No.E1G0241001(to XZ)。
文摘Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.
基金This work was supported by the National Nature Science Foundation of China grant 82170978(to K.J.)the Distinguished Young Scientists Funds of Shannxi Province 2021JC-34(to K.J.).
文摘Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金Gansu Province Youth Science and Technology Fund Project No.21JR7RA529Gansu Provincial Natural Science Foundation Project No.22JR5RA6182022 National Famous Traditional Chinese Medicine Expert Sun Qibin Inheritance Studio Construction Project,Chinese Medicine Teaching Letter(2022)No.75.
文摘Neurogenic bladder (NB) mainly occurs in patients with spinal cord injury (SCI). The pathological basis of NB is the occurrence of lesions in the urination control center, which requires systematic treatment. Western medicine has many treatment methods for this disease, which can alleviate the symptoms of the disease. However, the radical effect is not ideal and there are many adverse reactions. In comparison, acupuncture can improve the residual urine volume of NB patients and regulate the related indexes of urodynamics. There are many kinds of acupuncture therapies, such as simple acupuncture and moxibustion, which can comprehensively improve the therapeutic effect and obtain a better disease prognosis. Therefore, this article elaborates on the pathogenesis of SCI complicated with NB, the treatment mechanism, and treatment methods of acupuncture and moxibustion to provide a reference for clinical treatment.
文摘Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.
基金Supported by National Natural Science Foundation of China:82274666,82205255Natural Science Foundation of Hunan Province:2022JJ30036,2022JJ40312,20221140301+1 种基金Research Project of Education Department of Hunan Province:20C1432,21B0369Discipline of Integrated Traditional Chinese and Western Medicine of Hunan Province:2020ZXYJH23。
文摘Objective:To elucidate the underlying mechanism and effect of electroacupuncture(EA)on the neurogenic bladder following suprasacral spinal cord injury(ssCI).A rat model of detrusor hyperreflexia after SsCI was established to examine the urodynamics,detrusor muscle tissue morphology,the protein and mRNA expression levels of pituitary adenylate cyclase activating peptide(PACAP)and its receptor PAC1R,and cyclic adenosine monophosphate(cAMP)content in the detrusor muscle with a focus on the PACAPcAMP signaling pathway.Method:A total of 72 female SD rats were randomized into control group and sham operation group(n=12 per group)by using a random number table.The remaining 48 rats were established into the model of detrusor hyperreflexia after SsCI.After successful modeling,these rats were randomly assigned to model,EA,and EA+PACAP6-38 groups(n=12 per group).The unsuccessful modeled rats were used for exploratory observation.For the rats in EA group,"Ciliao(BL32)""Zhongji(CV3)",and"Sanyinjiao(SP6)"were needled and stimulated by EA.The PACAP receptor antagonist PACAP6-38 was administered intraperitoneally in the EA+PACAP6-38 group before EA,and EA was applied for seven consecutive days.After treatment,the urodynamics of the rats were analyzed,and hematoxylin and eosin staining was used to examine rat bladder detrusor tissue morphology.The expressions of PACAP-38 and PAC1R were detected by immunohistochemistry and Western blot.The mRNA expression levels of PACAP-38 and PAC1R were examined by RT-qPCR,while cAMP content was detected by ELISA.Results:(1)Compared with sham operation group,it was exhibited disarray in the transitional epithelium cells of the bladder in the modeled rats.The intercellular space was significantly widened,accompanied by inflammatory cell infiltration and noticeable tissue edema.Both the bladder initial pressure and leak point pressure of the rats were higher(P<0.01),whereas the maximum cystometric capacity and bladder compliance were lower(P<0.01).The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle,together with the cAMP content,were lower(P<0.05).(2)Compared with the model rats,the EA group showed reduced inflammatory response in the detrusor muscle tissue,with decreased monocyte infiltration and less severe tissue edema.The bladder smooth muscle cells exhibited increased integrity,and there was decreased cellular tissue edema,inflammatory cell infiltration,and fibroplasia.The bladder initial pressure and leak point pressure were lower(P<0.05),while the maximum cystometric capacity and bladder compliance were higher(P<0.01).The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle,along with the cAMP content,were higher(P<0.05).(3)Compared to the EA group,the EA+PACAP6-38 group showed a less organized arrangement of muscle fibers in the detrusor muscle tissue,larger intercellular space,monocyte infltration,and considerable tissue edema.The changes in bladder initial pressure and leak point pressure were not significant(P>0.05),while the maximum cystometric capacity and bladder compliance were lower(P<0.05).The changes in the protein and mRNA expressions of PACAP-38 within the detrusor muscle were not signifcant(P>0.05),whereas the protein and mRNA expressions of PAC1R were reduced(P<0.05),and the cAMP content within the detrusor muscle was lower(P<0.05).Conclusion:EA can ameliorate the uninhibited contractile condition of the detrusor muscle in the bladder following SSCI.By mediating the PACAP-cAMP signaling pathway,it reduces the pathological damage to the detrusor muscle,thereby improving bladder function.
基金supported by the National Glaucoma Research Program of the Bright Focus Foundationsupported by an unrestricted research grant from Research to Prevent BlindnessNIH center grant EY014801
文摘Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.
文摘Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflam- matory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.
