BACKGROUND Acute cerebral infarction(ACI),a leading cause of death and disability,causes brain ischemia due to vessel blockage.Current time-limited interventions,such as clot removal,often fail to restore full functio...BACKGROUND Acute cerebral infarction(ACI),a leading cause of death and disability,causes brain ischemia due to vessel blockage.Current time-limited interventions,such as clot removal,often fail to restore full function.Neurorestoration is vital,but complicated.Vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)promote angiogenesis and neuroprotection.Stem cell therapy has potential to promote neurorestoration.Specifically,neural stem cells(NSC)reconstruct neural tissue,while mesenchymal stem cells(MSCs)provide support and secrete beneficial factors.Combining NSCs and MSCs in stem cell therapy may synergistically enhance ACI recovery,potentially via the regulation of VEGF and bFGF.However,the mechanisms underlying this combined approach remain unclear.AIM To investigate the therapeutic effect of combined NSC and MSC transplantation on neurological recovery and bFGF/VEGF expression in ACI patients.METHODS This study enrolled 156 patients with ACI treated from June 2022 to June 2023.Patients were randomly assigned to two groups:The control group(n=78)received conventional drug therapy,while the observation group(n=78)received conventional therapy and combined NSC and MSC transplantation.The following outcomes were compared between groups:National Institutes of Health Stroke Scale(NIHSS)score,Barthel index,cerebral perfusion and diffusion on magnetic resonance imaging,serum bFGF and VEGF levels,clinical efficacy,and adverse events.RESULTS Serum VEGF and bFGF levels negatively correlated with NIHSS scores in patients with ACI(r=-0.388,r=-0.239;P<0.05).The observation group(NSC and MSC)showed a significantly higher clinical efficacy of treatment than the controls(85.9%vs 69.2%;P<0.05).Both groups showed improved cerebral perfusion,increased Barthel index,and decreased NIHSS scores post-treatment(P<0.05),with significantly greater improvements in the observation group.Serum VEGF and bFGF levels increased significantly in both groups(P<0.05),but were higher in the observation group.Adverse events in the observation group(transient fever:4 cases;agitation:1 case;headache:2 cases)were mild and resolved with symptomatic treatment.Six-month follow-up revealed no abnormalities in magnetic resonance imaging,electrocardiogram,or blood tests.CONCLUSION NSC-MSC combination therapy enhances neurological function and cerebral perfusion in patients with ACI by upregulating VEGF and bFGF expression,demonstrating favorable clinical efficacy and safety.展开更多
BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pe...BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pediatric populations remains under-researched,with challenges in diagnosis and management AIM To synthesize the current literature on FND in children,focusing on clinical presentation,diagnostic approaches,treatment strategies,and outcomes.METHODS A comprehensive literature search was conducted across multiple databases,including PubMed,Scopus,and Web of Science,for articles published up to August 2024.Studies were included if they addressed FND in pediatric populations,specifically focusing on review articles,research articles,systematic reviews,meta-analyses,case reports,guidelines,expert opinions,and editorials.Data extraction and quality assessment were performed according to PRISMA guidelines.A total of 308 articles were included in the final analysis.RESULTS The analysis included 189 review articles,57 research articles,3 systematic reviews and meta-analyses,5 case reports,2 guidelines,5 expert opinions,and 2 editorials.Key findings revealed a broad spectrum of symptoms,including motor and sensory disturbances and psychological factors contributing to the onset and persistence of FND.Diagnostic challenges were frequently highlighted,emphasizing the need for interdisciplinary approaches.Treatment strategies varied,with cognitive-behavioral therapy(CBT)and multidisciplinary care emerging as the most effective approaches.The outcomes varied,with early intervention being critical for a better prognosis.CONCLUSION Early diagnosis and multidisciplinary care,including CBT,are critical for improving outcomes in pediatric FND.Standardized diagnostic criteria and treatment protocols are needed to enhance clinical management.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.展开更多
Objective:To analyze the application effectiveness of the integrated medical-nursing comprehensive care model in cases of cerebral infarction and clarify its clinical practical value for the patient rehabilitation pro...Objective:To analyze the application effectiveness of the integrated medical-nursing comprehensive care model in cases of cerebral infarction and clarify its clinical practical value for the patient rehabilitation process.Methods:A total of 60 patients with cerebral infarction admitted from June 2024 to December 2024 were selected as the research subjects and randomly divided into a control group and a research group,with 30 cases in each group.Patients in the control group received routine clinical nursing measures,while those in the study group underwent collaborative healthcare intervention in addition to routine nursing.The intervention included joint disease assessment,personalized rehabilitation training guidance,psychological counseling,and continuous nursing services after discharge.A comparative study was conducted by evaluating indicators such as the scores on adverse emotion scales,the extent of neurological recovery,the effectiveness rate of clinical rehabilitation treatment,and the level of satisfaction with nursing services between the two groups.Results:After the intervention,the scores on the Self-Rating Anxiety Scale(SAS)and the Self-Rating Depression Scale(SDS)in the study group decreased to(40.12±5.01)and(41.36±5.20),respectively,both significantly lower than those in the control group,which were(47.36±5.82)and(48.95±5.63),respectively.The differences between the two groups were statistically significant(p<0.05).The improvement in the neurological deficit scores of patients in the study group reached(9.18±2.04),higher than that in the control group,which was(5.17±1.82)(p<0.05).The overall clinical rehabilitation effectiveness rate in the study group was 93.3%,significantly higher than that in the control group,which was 73.3%.The satisfaction rate with nursing services in the study group reached 96.7%,also higher than that in the control group,which was 83.3%.The differences between the two groups were statistically significant(p<0.05).Conclusion:The integrated healthcare nursing model can effectively alleviate adverse emotional states in patients with cerebral infarction,facilitate the repair and reconstruction of neurological function,improve the effectiveness of clinical rehabilitation treatment and satisfaction with nursing services,and thus holds high value for clinical promotion and application.展开更多
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in...Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.展开更多
Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv...Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.展开更多
Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regula...Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regulate the inflammatory response.Therefore,it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects.In this study,we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks.The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats.Subsequently,we performed left stellate ganglion block with 1%lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion.Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content.It also improved the recovery of neurological function,increased 28-day survival rate,inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats.However,injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block,whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect.We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke.These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway.We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-...Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke （59.6%） was the primary stroke type found in the young group, while ischemic stroke （60.0%） was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction （such as friendship） improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.展开更多
The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues,...The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia.展开更多
Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their appli...Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.展开更多
Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium stat...Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.展开更多
BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulatio...BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.展开更多
Fluorescent neuronal tracers should not be toxic to the nervous system when used in long-term labeling. Previous studies have addressed tracer toxicity, but whether tracers injected into an intact nerve result in func...Fluorescent neuronal tracers should not be toxic to the nervous system when used in long-term labeling. Previous studies have addressed tracer toxicity, but whether tracers injected into an intact nerve result in functional impairment remains to be elucidated. In the present study, we examined the functions of motor, sensory and autonomic nerves following the application of 5% Fluoro-Gold, 4% True Blue and 10% Fluoro-Ruby （5 pL） to rat tibial nerves via pressure injection. A set of evaluation methods including walking track analysis, plantar test and laser Doppler perfusion imaging was used to determine the action of the fluorescent neuronal tracers. Additionally, nerve pathology and ratio of muscle wet weight were also observed. Results showed that injection of Fluoro-Gold significantly resulted in loss of motor nerve function, lower plantar sensibility, increasing blood flow volume and higher neurogenic vasodilatation. Myelinated nerve fiber degeneration, unclear boundaries in nerve fibers and high retrograde labeling efficacy were observed in the Fluoro-Gold group. The True Blue group also showed obvious neurogenic vasodilatation, but less severe loss of motor function and degeneration, and fewer labeled motor neurons were found compared with the Fluoro-Gold group. No anomalies of motor and sensory nerve function and no myelinated nerve fiber degeneration were observed in the Fluoro-Ruby group. Experimental findings indicate that Fluoro-Gold tracing could lead to significant functional impairment of motor, sensory and autonomic nerves, while functional impairment was less severe following True Blue tracing. Fluoro-Ruby injection appears to have no effect on neurological function.展开更多
A variety of inlfammatory cytokines are involved in spinal cord injury and inlfuence the recov-ery of neuronal function. In the present study, we established a rat model of acute spinal cord injury by cerclage. The ce...A variety of inlfammatory cytokines are involved in spinal cord injury and inlfuence the recov-ery of neuronal function. In the present study, we established a rat model of acute spinal cord injury by cerclage. The cerclage suture was released 8 or 72 hours later, to simulate decompres-sion surgery. Neurological function was evaluated behaviorally for 3 weeks after surgery, and tumor necrosis factorα immunoreactivity and apoptosis were quantiifed in the region of injury. Rats that underwent decompression surgery had significantly weaker immunoreactivity of tumor necrosis factorα and signiifcantly fewer apoptotic cells, and showed faster improvement of locomotor function than animals in which decompression surgery was not performed. De-compression at 8 hours resulted in signiifcantly faster recovery than that at 72 hours. These data indicate that early decompression may improve neurological function after spinal cord injury by inhibiting the expression of tumor necrosis factorα.展开更多
Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple pro...Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.展开更多
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.展开更多
Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients w...Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients with acute cerebral infarction. Methods: The patients with acute cerebral infarction who were admitted to our hospital between April 2015 and October 2018 and with the onset time 4.5 hours were selected and divided into the observation group receiving butyphthalide + rt-PA intravenous thrombolysis and the control group receiving rt-PA intravenous thrombolysis by random number table. The differences in DWI parameter apparent diffusion coefficient (ADC), coagulation function indexes and neurological function indexes were compared between the two groups. Results: At 7 and 14 days after treatment, the ADC values of both groups were significantly increased, and the ADC values of the observation group were significantly higher than those of the control group;at 7 days after treatment, the prothrombin time (PT) and activated partial thromboplastin time (APTT) levels in both groups were significantly prolonged whereas fibrinogen (FIB), D-dimer (D-D), platelet activating factor (PAF), P-selectin, von Willebrand factor (vWF), neuron-specific enolase (NSE), S100B protein (S100B), malondialdehyde (MDA) and endothelin-1 (ET-1) contents were significantly decreased, and the APTT and PT levels in the observation group were significantly shorter than those in the control group whereas FIB, D-D, PAF, P-selectin, vWF, NSE, S100B, MDA and ET-1 contents were significantly lower than those in the control group. Conclusion: Butyphthalide + rt-PA intravenous thrombolysis can improve the DWI characteristics, coagulation function and neurological function of patients with acute cerebral infarction.展开更多
Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A...Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A total of 96 patients with acute cerebral infarction admitted to our hospital from September 2017 to October 2019 were randomly divided into two groups,with 48 patients in each group.The control group(n=48)received routine treatment,and the observation group received intravenous thrombolysis therapy with alteplase on the basis of routine treatment.The neurological deficit score,prothrombin time(PT),activated partial thromboplastin time(APTT),tumor necrosis factor-a level(TNF-α),and high-sensitivity C-reactive protein(hs-CRP)were compared between the two groups after 15 days of treatment.Results:After treatment,NIHSS scores in both groups were lower than those before treatment;PT levels were increased,while APTT,TNF-αand hs-CRP levels were all decreased in both groups,and the changes in the observation group were greater than those in the control group,with statistically significant difference(P<0.05).Conclusions:Intravenous thrombolysis therapy with alteplase can improve the neurological function,coagulation function and serum levels of inflammatory factors in patients with acute cerebral infarction,which is worthy of clinical application.展开更多
文摘BACKGROUND Acute cerebral infarction(ACI),a leading cause of death and disability,causes brain ischemia due to vessel blockage.Current time-limited interventions,such as clot removal,often fail to restore full function.Neurorestoration is vital,but complicated.Vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)promote angiogenesis and neuroprotection.Stem cell therapy has potential to promote neurorestoration.Specifically,neural stem cells(NSC)reconstruct neural tissue,while mesenchymal stem cells(MSCs)provide support and secrete beneficial factors.Combining NSCs and MSCs in stem cell therapy may synergistically enhance ACI recovery,potentially via the regulation of VEGF and bFGF.However,the mechanisms underlying this combined approach remain unclear.AIM To investigate the therapeutic effect of combined NSC and MSC transplantation on neurological recovery and bFGF/VEGF expression in ACI patients.METHODS This study enrolled 156 patients with ACI treated from June 2022 to June 2023.Patients were randomly assigned to two groups:The control group(n=78)received conventional drug therapy,while the observation group(n=78)received conventional therapy and combined NSC and MSC transplantation.The following outcomes were compared between groups:National Institutes of Health Stroke Scale(NIHSS)score,Barthel index,cerebral perfusion and diffusion on magnetic resonance imaging,serum bFGF and VEGF levels,clinical efficacy,and adverse events.RESULTS Serum VEGF and bFGF levels negatively correlated with NIHSS scores in patients with ACI(r=-0.388,r=-0.239;P<0.05).The observation group(NSC and MSC)showed a significantly higher clinical efficacy of treatment than the controls(85.9%vs 69.2%;P<0.05).Both groups showed improved cerebral perfusion,increased Barthel index,and decreased NIHSS scores post-treatment(P<0.05),with significantly greater improvements in the observation group.Serum VEGF and bFGF levels increased significantly in both groups(P<0.05),but were higher in the observation group.Adverse events in the observation group(transient fever:4 cases;agitation:1 case;headache:2 cases)were mild and resolved with symptomatic treatment.Six-month follow-up revealed no abnormalities in magnetic resonance imaging,electrocardiogram,or blood tests.CONCLUSION NSC-MSC combination therapy enhances neurological function and cerebral perfusion in patients with ACI by upregulating VEGF and bFGF expression,demonstrating favorable clinical efficacy and safety.
文摘BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pediatric populations remains under-researched,with challenges in diagnosis and management AIM To synthesize the current literature on FND in children,focusing on clinical presentation,diagnostic approaches,treatment strategies,and outcomes.METHODS A comprehensive literature search was conducted across multiple databases,including PubMed,Scopus,and Web of Science,for articles published up to August 2024.Studies were included if they addressed FND in pediatric populations,specifically focusing on review articles,research articles,systematic reviews,meta-analyses,case reports,guidelines,expert opinions,and editorials.Data extraction and quality assessment were performed according to PRISMA guidelines.A total of 308 articles were included in the final analysis.RESULTS The analysis included 189 review articles,57 research articles,3 systematic reviews and meta-analyses,5 case reports,2 guidelines,5 expert opinions,and 2 editorials.Key findings revealed a broad spectrum of symptoms,including motor and sensory disturbances and psychological factors contributing to the onset and persistence of FND.Diagnostic challenges were frequently highlighted,emphasizing the need for interdisciplinary approaches.Treatment strategies varied,with cognitive-behavioral therapy(CBT)and multidisciplinary care emerging as the most effective approaches.The outcomes varied,with early intervention being critical for a better prognosis.CONCLUSION Early diagnosis and multidisciplinary care,including CBT,are critical for improving outcomes in pediatric FND.Standardized diagnostic criteria and treatment protocols are needed to enhance clinical management.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
基金Science and Technology Support Program Project of Baoding City,Hebei Province(Project No.:2541ZF107)。
文摘Objective:To analyze the application effectiveness of the integrated medical-nursing comprehensive care model in cases of cerebral infarction and clarify its clinical practical value for the patient rehabilitation process.Methods:A total of 60 patients with cerebral infarction admitted from June 2024 to December 2024 were selected as the research subjects and randomly divided into a control group and a research group,with 30 cases in each group.Patients in the control group received routine clinical nursing measures,while those in the study group underwent collaborative healthcare intervention in addition to routine nursing.The intervention included joint disease assessment,personalized rehabilitation training guidance,psychological counseling,and continuous nursing services after discharge.A comparative study was conducted by evaluating indicators such as the scores on adverse emotion scales,the extent of neurological recovery,the effectiveness rate of clinical rehabilitation treatment,and the level of satisfaction with nursing services between the two groups.Results:After the intervention,the scores on the Self-Rating Anxiety Scale(SAS)and the Self-Rating Depression Scale(SDS)in the study group decreased to(40.12±5.01)and(41.36±5.20),respectively,both significantly lower than those in the control group,which were(47.36±5.82)and(48.95±5.63),respectively.The differences between the two groups were statistically significant(p<0.05).The improvement in the neurological deficit scores of patients in the study group reached(9.18±2.04),higher than that in the control group,which was(5.17±1.82)(p<0.05).The overall clinical rehabilitation effectiveness rate in the study group was 93.3%,significantly higher than that in the control group,which was 73.3%.The satisfaction rate with nursing services in the study group reached 96.7%,also higher than that in the control group,which was 83.3%.The differences between the two groups were statistically significant(p<0.05).Conclusion:The integrated healthcare nursing model can effectively alleviate adverse emotional states in patients with cerebral infarction,facilitate the repair and reconstruction of neurological function,improve the effectiveness of clinical rehabilitation treatment and satisfaction with nursing services,and thus holds high value for clinical promotion and application.
基金supported by the National Natural Science Foundation of China,No.81574042the Traditional Chinese Medicine Special Research Projects of Henan Province of China,No.2018JDZX011(both to XDF).
文摘Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.
基金The study was approved by Postdoctoral Scientific Research Developmental Fund of Heilongjiang Province,No.LBH-Q18074(to WCY).
文摘Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regulate the inflammatory response.Therefore,it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects.In this study,we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks.The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats.Subsequently,we performed left stellate ganglion block with 1%lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion.Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content.It also improved the recovery of neurological function,increased 28-day survival rate,inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats.However,injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block,whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect.We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke.These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway.We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
基金supported by the Special Fund of Basic Scientific Research Service Fee of Central Public Welfare Scientif ic Research Institute of China,No.2014CZ-13
文摘Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke （59.6%） was the primary stroke type found in the young group, while ischemic stroke （60.0%） was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction （such as friendship） improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.
基金supported by the Combined pecific Foundation of Department of Science and Technology of Yunnan Province and Kunming Medical University,No.2008CD037
文摘The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia.
基金supported by the National Natural Science Foundation of China,No.31171038the Natural Science Foundation of Jiangsu Province of China,No.BK2011385+3 种基金the "333" Program Funding of Jiangsu Province of China,No.BRA2016450the Training Program of Innovation and Entrepreneurship for Undergraduates of Nantong University of China,No.201510304033Z,201610304053Zthe Training Program of Innovation and Entrepreneurship for Graduates of Nantong University of China,No.YKC14050,YKC15046a grant from Funds for the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.
文摘Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.
基金National Natural Science Foundation of China,No.81774059 and No.82074533Tianjin Natural Science Foundation,No.19JCZDJC37100.
文摘BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.
基金financially supported by the National High-Tech Research and Development Program of China(863 Program),No.2012AA020502the National Natural Science Foundation of China,No.81100939 and 81130080+2 种基金the Collegiate Natural Science Foundation of Jiangsu Province,No.10KJB310009the Innovation Program for Collegiate Postgraduates of Jiangsu Province,No.CXZZ12_0872the Qinglan Project of Jiangsu Province
文摘Fluorescent neuronal tracers should not be toxic to the nervous system when used in long-term labeling. Previous studies have addressed tracer toxicity, but whether tracers injected into an intact nerve result in functional impairment remains to be elucidated. In the present study, we examined the functions of motor, sensory and autonomic nerves following the application of 5% Fluoro-Gold, 4% True Blue and 10% Fluoro-Ruby （5 pL） to rat tibial nerves via pressure injection. A set of evaluation methods including walking track analysis, plantar test and laser Doppler perfusion imaging was used to determine the action of the fluorescent neuronal tracers. Additionally, nerve pathology and ratio of muscle wet weight were also observed. Results showed that injection of Fluoro-Gold significantly resulted in loss of motor nerve function, lower plantar sensibility, increasing blood flow volume and higher neurogenic vasodilatation. Myelinated nerve fiber degeneration, unclear boundaries in nerve fibers and high retrograde labeling efficacy were observed in the Fluoro-Gold group. The True Blue group also showed obvious neurogenic vasodilatation, but less severe loss of motor function and degeneration, and fewer labeled motor neurons were found compared with the Fluoro-Gold group. No anomalies of motor and sensory nerve function and no myelinated nerve fiber degeneration were observed in the Fluoro-Ruby group. Experimental findings indicate that Fluoro-Gold tracing could lead to significant functional impairment of motor, sensory and autonomic nerves, while functional impairment was less severe following True Blue tracing. Fluoro-Ruby injection appears to have no effect on neurological function.
基金supported by a grant from the Anhui Provincial Health Department-Funded Medical Research Project in 2009 in China,No.09C33a grant from the Key Scientific Research Project of Cultivating Fund of Wannan Medical College in China,No.WK2014ZF14
文摘A variety of inlfammatory cytokines are involved in spinal cord injury and inlfuence the recov-ery of neuronal function. In the present study, we established a rat model of acute spinal cord injury by cerclage. The cerclage suture was released 8 or 72 hours later, to simulate decompres-sion surgery. Neurological function was evaluated behaviorally for 3 weeks after surgery, and tumor necrosis factorα immunoreactivity and apoptosis were quantiifed in the region of injury. Rats that underwent decompression surgery had significantly weaker immunoreactivity of tumor necrosis factorα and signiifcantly fewer apoptotic cells, and showed faster improvement of locomotor function than animals in which decompression surgery was not performed. De-compression at 8 hours resulted in signiifcantly faster recovery than that at 72 hours. These data indicate that early decompression may improve neurological function after spinal cord injury by inhibiting the expression of tumor necrosis factorα.
基金supported by the National Natural Science Foundation of China(Nos.32000692 and 32200816).
文摘Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
基金Major Project of Shanghai Science and Technology Commission (Sub-project) No: 11411950300
文摘Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients with acute cerebral infarction. Methods: The patients with acute cerebral infarction who were admitted to our hospital between April 2015 and October 2018 and with the onset time 4.5 hours were selected and divided into the observation group receiving butyphthalide + rt-PA intravenous thrombolysis and the control group receiving rt-PA intravenous thrombolysis by random number table. The differences in DWI parameter apparent diffusion coefficient (ADC), coagulation function indexes and neurological function indexes were compared between the two groups. Results: At 7 and 14 days after treatment, the ADC values of both groups were significantly increased, and the ADC values of the observation group were significantly higher than those of the control group;at 7 days after treatment, the prothrombin time (PT) and activated partial thromboplastin time (APTT) levels in both groups were significantly prolonged whereas fibrinogen (FIB), D-dimer (D-D), platelet activating factor (PAF), P-selectin, von Willebrand factor (vWF), neuron-specific enolase (NSE), S100B protein (S100B), malondialdehyde (MDA) and endothelin-1 (ET-1) contents were significantly decreased, and the APTT and PT levels in the observation group were significantly shorter than those in the control group whereas FIB, D-D, PAF, P-selectin, vWF, NSE, S100B, MDA and ET-1 contents were significantly lower than those in the control group. Conclusion: Butyphthalide + rt-PA intravenous thrombolysis can improve the DWI characteristics, coagulation function and neurological function of patients with acute cerebral infarction.
文摘Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A total of 96 patients with acute cerebral infarction admitted to our hospital from September 2017 to October 2019 were randomly divided into two groups,with 48 patients in each group.The control group(n=48)received routine treatment,and the observation group received intravenous thrombolysis therapy with alteplase on the basis of routine treatment.The neurological deficit score,prothrombin time(PT),activated partial thromboplastin time(APTT),tumor necrosis factor-a level(TNF-α),and high-sensitivity C-reactive protein(hs-CRP)were compared between the two groups after 15 days of treatment.Results:After treatment,NIHSS scores in both groups were lower than those before treatment;PT levels were increased,while APTT,TNF-αand hs-CRP levels were all decreased in both groups,and the changes in the observation group were greater than those in the control group,with statistically significant difference(P<0.05).Conclusions:Intravenous thrombolysis therapy with alteplase can improve the neurological function,coagulation function and serum levels of inflammatory factors in patients with acute cerebral infarction,which is worthy of clinical application.
