Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation sys...Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.展开更多
Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectiou...Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Delirium is a transient and acute syndrome of encephalopathy,characterized by disturbances in consciousness,orientation,cognition,perception,and emotional regulation,often accompanied by hallucinations,illusions,psych...Delirium is a transient and acute syndrome of encephalopathy,characterized by disturbances in consciousness,orientation,cognition,perception,and emotional regulation,often accompanied by hallucinations,illusions,psychomotor agitation,and restlessness.Postoperative delirium(POD),a common complication particularly in elderly patients,significantly impacts recovery by prolonging mechanical ventilation,neurosurgical intensive care unit stays,and overall hospitalization durations,while severely diminishing patients’quality of life after discharge.Despite its prevalence,POD remains underrecognized in clinical practice,with significant gaps in its diagnosis and management.This review explores the definition,diagnostic criteria,underlying pathogenesis,and associated risk factors of POD in neurosurgical patients,aiming to offer valuable insights for improving clinical diagnosis and therapeutic strategies.展开更多
Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the cl...Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the clinical application of our neurosurgical HOR and propose a scale to score cases clearly.Methods We reviewed the operating procedures and duration of stay in 1865 HOR cases.The actual procedures of each case were summarized into 5 application types,and numerical assignment was used to distinguish the dependence of each type on our HOR:surgical procedures combined with interventional procedures(4 points,the highest dependence),surgical procedures combined with imaging procedures(3 points),interventional procedures(2 points),imaging procedures(1 point),and surgical procedures(0 points,the lowest dependence).Results A novel scale that could score 1865 cases into those 5 grades was developed.The percentages by grade were as follows:4 points,4.24%;3 points,4.88%;2 points,20.75%;1 point,69.38%;and 0 points,0.75%.The cumulative usage time was 4241.9 h,the duration of which was as follows:4 points,16.17%;3 points,15.50%;2 points,31.32%;1 point,35.62%;and 0 points,1.39%.Conclusions The HOR serves as a multifunctional room to treat neurosurgical diseases.The scale helps to quickly prioritize cases that rely more on HOR,providing guidelines for surgical scheduling.Although our HOR is unsuitable for emergency cases,it clearly shows the application performance of our HOR to provide a reference for promoting its efficient application.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocke...Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocked or damaged lymphatic vessels.In early 2024,Dr.Qingping Xie from Hangzhou Qiushi Hospital,China,and Dr.Wei F.Chen from the Cleveland Clinic,USA,adapted LVA for the treatment of patients with Alzheimer’s disease(AD).As a VIEWPOINT,they presented a video showcasing the post-surgery cognitive recovery of an 84-year-old AD patient(Xie et al.,2024).展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological...Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy a...A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.展开更多
Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammati...Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.展开更多
Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean r...Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Effective treatment of subcutaneous tumors remains a focal point in cancer therapy.Photothermal therapy,a novel therapeutic approach,has emerged as a promising alternative,offering a less invasive option for the treat...Effective treatment of subcutaneous tumors remains a focal point in cancer therapy.Photothermal therapy,a novel therapeutic approach,has emerged as a promising alternative,offering a less invasive option for the treatment of subcutaneous tumors.This study reports the exploration of novel supramolecular halogen-bonded organic frameworks(XOFs)based on[N…Br^(+)…N]halogen bonds through the ligand exchange strategy and their application in photothermal therapy.Through ligand exchange,XOF(Br)-TPy was successfully prepared,and its structure and properties were thoroughly characterized using NMR,XPS,FT-IR,and XRD techniques.Due to their cationic characteristics,these XOFs serve as effective carriers for the photothermal agent IR820.In vitro experiments demonstrated that the IR820@XOF(Br)-TPy composite exhibits excellent photothermal conversion efficiency under NIR irradiation,effectively inducing tumor cell ablation.Furthermore,in vivo studies confirmed the remarkable antitumor efficacy of the composite material in a subcutaneous tumor model.This work demonstrates that the ligand exchange strategy is a versatile and facile approach for constructing XOFs(Br)and provides a novel strategy for developing advanced photothermal therapeutic agents with significant application potential.展开更多
Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of opt...Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.展开更多
基金funded by National Natural Science Foundation of China(No.82272134)Innovative Research Group Project of the National Natural Science Foundation of China(No.82272134,Xiao-lei Chen).
文摘Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.
文摘Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金Supported by Science and Technology Program of Nantong City,No.Key003Nantong Young Medical Expert,No.46+2 种基金the Science and Technology Program of Nantong Health Committee,No.MA2019003,No.MA2021017,and No.MSZ2024038Science and Technology Program of Nantong City,No.JCZ2022040Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD022,and No.KD2024KYJJ289.
文摘Delirium is a transient and acute syndrome of encephalopathy,characterized by disturbances in consciousness,orientation,cognition,perception,and emotional regulation,often accompanied by hallucinations,illusions,psychomotor agitation,and restlessness.Postoperative delirium(POD),a common complication particularly in elderly patients,significantly impacts recovery by prolonging mechanical ventilation,neurosurgical intensive care unit stays,and overall hospitalization durations,while severely diminishing patients’quality of life after discharge.Despite its prevalence,POD remains underrecognized in clinical practice,with significant gaps in its diagnosis and management.This review explores the definition,diagnostic criteria,underlying pathogenesis,and associated risk factors of POD in neurosurgical patients,aiming to offer valuable insights for improving clinical diagnosis and therapeutic strategies.
基金supported by the Technology Innovation Special Major Project of Hubei Province(grant number 2022BCA003).
文摘Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the clinical application of our neurosurgical HOR and propose a scale to score cases clearly.Methods We reviewed the operating procedures and duration of stay in 1865 HOR cases.The actual procedures of each case were summarized into 5 application types,and numerical assignment was used to distinguish the dependence of each type on our HOR:surgical procedures combined with interventional procedures(4 points,the highest dependence),surgical procedures combined with imaging procedures(3 points),interventional procedures(2 points),imaging procedures(1 point),and surgical procedures(0 points,the lowest dependence).Results A novel scale that could score 1865 cases into those 5 grades was developed.The percentages by grade were as follows:4 points,4.24%;3 points,4.88%;2 points,20.75%;1 point,69.38%;and 0 points,0.75%.The cumulative usage time was 4241.9 h,the duration of which was as follows:4 points,16.17%;3 points,15.50%;2 points,31.32%;1 point,35.62%;and 0 points,1.39%.Conclusions The HOR serves as a multifunctional room to treat neurosurgical diseases.The scale helps to quickly prioritize cases that rely more on HOR,providing guidelines for surgical scheduling.Although our HOR is unsuitable for emergency cases,it clearly shows the application performance of our HOR to provide a reference for promoting its efficient application.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
基金supported by AG057842 from the National Institutes of Health,TRIBA/Physiology Faculty Startup Fund from Augusta University (to FF)the National Natural Science Foundation of China (82173384)(to MG)
文摘Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocked or damaged lymphatic vessels.In early 2024,Dr.Qingping Xie from Hangzhou Qiushi Hospital,China,and Dr.Wei F.Chen from the Cleveland Clinic,USA,adapted LVA for the treatment of patients with Alzheimer’s disease(AD).As a VIEWPOINT,they presented a video showcasing the post-surgery cognitive recovery of an 84-year-old AD patient(Xie et al.,2024).
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
基金supported by the CJD Foundation,USA,the Alzheimer Forschung Initiative(AFI)e.V.,Germany,and Werner-Otto-Stiftung,Germany(all to HCA),ChinaScholarship Council(grant#202108080249 to FS)Deutsche Forschungsgemeinschaft(DFG)CRC877“Proteolysis as a regulatory event in pathophysiology”(project A12 to MG),Slovene Research and InnovationAgency(grant number P4-0176 to VCS).
文摘Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
文摘A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
基金supported by Yunnan Provincial Science and Technology Department,Nos.202403AC100007(to NZ),202301AY070001-239(to JY)Yunnan Revitalization Talent Support Program,Nos.2019-069(to ZY)and 2019-300(to JY)+1 种基金the National Natural Science Foundation of China,Nos.32260196(to JY)a grant from Kunming Medical University,No.2024S085(to KL)。
文摘Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.
基金supported by the National Natural Science Foundation of China(Nos.21977058 and 82473840)the Key R&D Program of Jiangsu Province(No.BE2021677)+2 种基金China Postdoctoral Science Foundation(No.2018T110533)the Key Natural Science Foundation of Jiangsu Higher Education Institutions(No.20KJA350002)Jiangsu Province Innovation Project of Postgraduate Training(No.KYCX22_3380).
文摘Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
基金supported by the National Natural Science Foundation of China(Nos.22371218,82271518,21801194)Xianyang Bureau of Science and Technology(No.L2024-QCY-ZYYJJQ-260)+2 种基金The Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCFZ-2022-030)Guiding Projects of Traditional Chinese Medicine in 2023~2024 by Hubei Provincial Administration of Traditional Chinese Medicine(No.ZY2023F038)the support of the Core Facility of Wuhan University and the Large-scale Instrument and Equipment Sharing Foundation of Wuhan University。
文摘Effective treatment of subcutaneous tumors remains a focal point in cancer therapy.Photothermal therapy,a novel therapeutic approach,has emerged as a promising alternative,offering a less invasive option for the treatment of subcutaneous tumors.This study reports the exploration of novel supramolecular halogen-bonded organic frameworks(XOFs)based on[N…Br^(+)…N]halogen bonds through the ligand exchange strategy and their application in photothermal therapy.Through ligand exchange,XOF(Br)-TPy was successfully prepared,and its structure and properties were thoroughly characterized using NMR,XPS,FT-IR,and XRD techniques.Due to their cationic characteristics,these XOFs serve as effective carriers for the photothermal agent IR820.In vitro experiments demonstrated that the IR820@XOF(Br)-TPy composite exhibits excellent photothermal conversion efficiency under NIR irradiation,effectively inducing tumor cell ablation.Furthermore,in vivo studies confirmed the remarkable antitumor efficacy of the composite material in a subcutaneous tumor model.This work demonstrates that the ligand exchange strategy is a versatile and facile approach for constructing XOFs(Br)and provides a novel strategy for developing advanced photothermal therapeutic agents with significant application potential.
基金supported by a grant from the Russian Science Foundation,No.23-75-10041(to MY)。
文摘Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.
