This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected...This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsy-chological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke pa-tients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20–2.58), low education level (OR 2.45, 95% CI 1.65–3.64), depressive symptom (OR 1.69, 95% CI 1.09–2.61), obesity (OR 2.57, 95% CI 1.41–4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10–2.37) and cortex lesion (OR 1.55, 95% CI 1.04–2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.展开更多
Symptoms that are multidimensional and concurrent should be assessed from different dimensions and managed together. Few studies have evaluated concurrent and multidimensional symptoms in patients with stroke. Most st...Symptoms that are multidimensional and concurrent should be assessed from different dimensions and managed together. Few studies have evaluated concurrent and multidimensional symptoms in patients with stroke. Most studies of stroke focused on dysfunctions and complications. We hypothesize that patients with stroke have a heavy symptom burden within 1 year. This study aimed to describe multidimensional and concurrent symptoms within 1 year after stroke. This study recruited 230 patients with stroke from the Rehabilitation Department of Xuhui District Center Hospital of Shanghai and the Shanghai Sunshine Rehabilitation Center in China from March to September 2017. The patients＇ multidimensional symptom experience and symptom burden were analyzed using a self-made structured questionnaire and the influential factors for symptom burden were identified. The mean number of symptoms in patients with stroke was 11.7 ± 3.5. More than two thirds of the participants suffered from at least 10 co-occurring symptoms. Unilateral limb weakness had the highest prevalence and frequency. Participation restriction had the highest symptom dimensions of severity and distress. Lack of self-care ability（severity）, memory deterioration（frequency）, imbalance of body（distress）, moodiness（distress）, being unable to move limbs at will（distress）, shoulder pain（distress）, and slower response（frequency） were independent factors of the total symptom burden score. These findings can provide essential information for efficient symptom management of patients with stroke.展开更多
We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure s...We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure sensory syndrome (2), ataxic hemiparesis (3), dysarthria clumsy hand syndrome (3), and sensory- motor deficit (5). Nineteen out of the 23 patients presented with completed strokes on arrival to the hospital, and 4 (17%) developed evolving-stroke within 24 hours of stroke onset. A lacune corresponded to the acute stroke could be found in all patients on brain magnetic resonance imaging (MRI), and in 18 (78%) on brain computed tomography (CT). MRI showed additional subclinical or asymptomatic “silent brain infarctions or lacunes” (SBI) in 19 (83%) of 23 patients, and leuko-araiosis (LA) of moderate to severe degree (> grade 2) was present in 61% of patients although dementia was absent. Hypertension is the risk factor in 78% of cases followed by diabetes mellitus, smoking, and elevated plasma cholesterol level. Independence of the types of lacunar syndromes, patients with hypertension and diabetes mellitus are associated with high grade LA. None with normal blood pressure and plasma glucose had grade 3 or grade 4 LA (p < 0.05). In conclusion, evolving-stroke occurs in one- fifth of patients with “first-ever” lacunar infarct within the first 24 hours of stroke onset. SBI was found in 83% of cases. Hypertension and diabetes mellitus are associated with additional SBI and high grade LA. The severity of leuko-araiosis per se dictates the cerebrovascular risks.展开更多
BACKGROUND At present,the incidence rate of ischemic stroke in young people is increasing yearly,and the age of onset is increasingly young.Therefore,primary and secondary prevention of ischemic stroke in young people...BACKGROUND At present,the incidence rate of ischemic stroke in young people is increasing yearly,and the age of onset is increasingly young.Therefore,primary and secondary prevention of ischemic stroke in young people,especially secondary prevention,is particularly crucial.AIM We aimed to comprehensively evaluate risk factors for stroke recurrence in firstever young ischemic stroke(YIS)patients.METHODS The meta-analysis was used to quantitatively analyze the research results on risk factors for stroke recurrence in first-ever YIS patients both domestically and internationally.Stata12.0 software was used for heterogeneity testing,publication bias analysis,sensitivity analysis,and the calculation of combined odds ratios and 95%confidence intervals.RESULTS The odds ratio(OR)values of the relationship between hypertension and hyperlipidemia and recurrence of first-ever YIS were 1.54(1.05-2.26)and 1.12(1.00-1.25),respectively.The OR values of male sex,type 2 diabetes,smoking,drinking and YIS recurrence were 1.66(0.98-2.79),1.01(0.64-1.59),1.21(0.83-1.76),and 1.28(0.82-2.53),respectively.The relationship between male sex,type 2 diabetes,smoking,drinking and YIS recurrence was ambiguous.CONCLUSION Hypertension and hyperlipidemia are important risk factors for stroke recurrence in first-ever YIS patients,and active intervention should be taken.展开更多
Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and fac...Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke. Data collection for this longitudinal study was conducted at baseline through face-toface interviews and follow-up was completed every 3 months via telephone, beginning in 2010 and continuing through 2014. Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior. At baseline, 372 male patients were recruited into the study. Totally, 155(41.7%) of these patients stopped smoking for stroke, and 61(39.3%) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day. Exposure to environmental tobacco smoke at places outside of home and work(such as bars, restaurants)(HR, 2.34; 95% CI, 1.04–5.29, P=0.04), not having a spouse(HR, 0.12; 95% CI, 0.04–0.36; P=0.0002) and smoking at least 20 cigarettes per day before stroke(HR, 2.42; 95% CI, 1.14–5.14, P=0.02) were predictors of smoking relapse. It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke. Environmental tobacco smoke should be addressed by smoke-free policies in public places.展开更多
Many blood biomarkers are reportedly helpful for predicting post-stroke cognitive impairment(PSCI),but no biomarkers are widely used in clinical practice.The purpose of this study was to investigate the association be...Many blood biomarkers are reportedly helpful for predicting post-stroke cognitive impairment(PSCI),but no biomarkers are widely used in clinical practice.The purpose of this study was to investigate the association between the plasma immunoproteasome and patients’90-day prognosis after first-ever acute ischemic stroke.In our prospective,single-center study,259 patients with first-ever acute ischemic stroke were enrolled from the Department of Neurology,Fujian Provincial Hospital,China,from March to September 2014.Of these,27 patients(10.4%)had unfavorable outcomes as assessed by the Modified Rankin Scale(scores of 3–6).The National Institutes of Health Stroke Scale score on admission,plasma N-terminal pro-B-type natriuretic peptide(NT-pro-BNP)levels,and immunopro-teasome subunit(low molecular mass peptide[LMP]2,LMP5,and LMP7)levels were significantly higher in the unfavorable outcome group than in the favorable outcome group.To predict unfavorable outcomes,the optimal cutoff points were National Institutes of Health Stroke Scale score>12,NT-pro-BNP level>1883.5 pg/mL,and LMP2 level>841.4 pg/mL.Of the 193 patients that were able to complete the Mini-Mental State Examination at 90 days poststroke,66 patients(34.2%)had PSCI.Plasma levels of NT-pro-BNP and LMP2 were higher in patients with PSCI than in those without PSCI.To predict PSCI,the optimal cutoff values were age>70.5 years and LMP2 level>630.5 pg/mL.These findings indicate that plasma LMP2 may serve as a new prognostic biomarker of poor outcome and PSCI at 90 days after stroke.This study was approved by the Ethics Committee of Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University(approval No.K2014-01-003)on January 15,2014.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Summary:Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence.However,the relationship between lesion locations and stroke rec...Summary:Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence.However,the relationship between lesion locations and stroke recurrence is unclear.We conducted a prospective cohort study of first-ever ischemic stroke survivors who were consecutively enrolled from January 2010 to December 2015.Stroke recurrence was assessed every 3 months after post-discharge via telephone interviews by trained interviewers.Lesion locations were obtained from hospital-based MRI or CT scans and classified using two classification systems that were based on cerebral hemisphere or vascular territory and brain anatomical structures.Flexible parametric survival models using the proportional hazards scale(PH model)were used to analyze the time-to-event data.Among 633 survivors,63.51%(n-402)had anterior circulation ischemia(ACI),and morc than half of all ACIs occurred in the subcortex.After a median follow-up of 2.5 years,117(18.48%)survivors developed a recurrent stroke.The results of the multivariate PH model showed that survivors with non-brain lesions were at higher risk of recurrence than those with right-side lesions(HR,2.79;95%CI,1.53,5.08;P-0.001).There was no increase in risk among survivors with left-side lesions(HR,0.97;95%CI,0.53,1.75;P=0.914)or both-side lesions(HR,1.24;95%CI,0.75,2.07;P-0.401)compared to those with right-side lesions.Additionally,there were no associations between stroke ecurrence and lesion locations that were classified based on vascular territory and brain anatomical structures.It was concluded that first-ever ischemic stroke survivors with non-brain lesion had higher recurrence risk than those with right-side lesion,although no significant associations were found when the lesion locations were classified by vascular territory and brain anatomical structures.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of r...Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of reactive oxygen species in the brain,all of which reflect a dynamic process of change.This complexity hinders achievement of significant therapeutic outcomes with standard stroke treatment procedures,limiting post-stroke recovery.This review presents an innovative post-stroke therapeutic approach that utilizes nanomedicines to modify the cerebral microenvironment.It highlights the primary roles of chronic inflammation and nerve repair issues in causing prolonged impairment in stroke patients.Traditional therapies show limited effectiveness in achieving neuroprotection,immunoregulation,and neural regeneration during the subacute and chronic phases of stroke.Therefore,effective stroke management requires the use of specific therapeutic strategies tailored to the pathological characteristics of each phase.Various types of nanomedicines possess distinct physicochemical properties and can be selected on the basis of the specific therapeutic needs.Surface-modification technologies have significantly enhanced the ability of nanomedicines to penetrate the blood-brain barrier and improve their targeting capabilities in drug administration.However,the stability,biocompatibility,and long-term safety of nanomedicines require further optimization for clinical application.Nanomedicines represent a novel approach to stroke treatment through targeted delivery and multifaceted regulatory mechanisms.These medicines provide distinct advantages,particularly in addressing chronic inflammation and promoting nerve regeneration.As a result,nanomedicines are expected to significantly improve rehabilitation outcomes and quality of life for stroke patients in the future,emerging as a crucial modality for stroke treatment.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
Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fun...Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.展开更多
Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune respons...Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.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
Objective Stroke is the third leading cause of death worldwide,with the highest incidence in Asia,particularly in China,where smoking remains a major risk factor.The smoking prevalence in China is similar to that in A...Objective Stroke is the third leading cause of death worldwide,with the highest incidence in Asia,particularly in China,where smoking remains a major risk factor.The smoking prevalence in China is similar to that in Asia.Whether the risk estimates for smoking-related stroke in China and all Asian countries are still unknown which is worth evaluating.Thus,this study aims to compare the Relative Risk(RR)of smoking-attributed stroke among the Chinese and Asian populations.Methods A literature search was conducted from the inception to September 10,2022.Studies meeting the criteria were included.The articles were screened,and related information was extracted.Pooled RRs stratified by smoking status and sex were analyzed,including subgroup analyses for China,other Asian countries,and Asia overall.Finally,publication bias and sensitivity analyses were conducted.Results Thirty-seven articles on the Chinese population and 15 on other Asian populations were included,with a mean Newcastle-Ottawa scale(NOS)score of 7.25.About ever smokers,there had no statistical difference existed in both sexes and females between China and other Asian countries,while the RR of males in other Asian countries[2.31(1.38,3.86)]was higher than that in China[1.21(1.15,1.26)];further subgroup analysis indicated that other Asian countries had higher RR[3.76(3.02,4.67)]in the morbidity subgroup.The RRs of both sexes,males and females,between China and the whole of Asia were not statistically different.As for current and former smokers,no meaningful statistical difference was observed in the pooled RRs of both sexes,males and females,in China,other Asian countries,and all of Asia.Conclusion The RR of males ever smokers in China was smaller than that in other Asian countries due to the few articles of morbidity subgroup,but had no statistical difference with the whole of Asia;other groups of ever smokers,current smokers,and former smokers were not statistically significant with other Asian countries or the whole of Asia.展开更多
While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the assoc...While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.展开更多
基金supported by grants from Bayer Healthcare,Co., Ltd.,GermanyEisai Co.,Ltd.,Japan
文摘This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsy-chological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke pa-tients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20–2.58), low education level (OR 2.45, 95% CI 1.65–3.64), depressive symptom (OR 1.69, 95% CI 1.09–2.61), obesity (OR 2.57, 95% CI 1.41–4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10–2.37) and cortex lesion (OR 1.55, 95% CI 1.04–2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.
基金supported by the Fuxing Nursing Research Foundation of Fudan University of China,No.FNF201611
文摘Symptoms that are multidimensional and concurrent should be assessed from different dimensions and managed together. Few studies have evaluated concurrent and multidimensional symptoms in patients with stroke. Most studies of stroke focused on dysfunctions and complications. We hypothesize that patients with stroke have a heavy symptom burden within 1 year. This study aimed to describe multidimensional and concurrent symptoms within 1 year after stroke. This study recruited 230 patients with stroke from the Rehabilitation Department of Xuhui District Center Hospital of Shanghai and the Shanghai Sunshine Rehabilitation Center in China from March to September 2017. The patients＇ multidimensional symptom experience and symptom burden were analyzed using a self-made structured questionnaire and the influential factors for symptom burden were identified. The mean number of symptoms in patients with stroke was 11.7 ± 3.5. More than two thirds of the participants suffered from at least 10 co-occurring symptoms. Unilateral limb weakness had the highest prevalence and frequency. Participation restriction had the highest symptom dimensions of severity and distress. Lack of self-care ability（severity）, memory deterioration（frequency）, imbalance of body（distress）, moodiness（distress）, being unable to move limbs at will（distress）, shoulder pain（distress）, and slower response（frequency） were independent factors of the total symptom burden score. These findings can provide essential information for efficient symptom management of patients with stroke.
文摘We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure sensory syndrome (2), ataxic hemiparesis (3), dysarthria clumsy hand syndrome (3), and sensory- motor deficit (5). Nineteen out of the 23 patients presented with completed strokes on arrival to the hospital, and 4 (17%) developed evolving-stroke within 24 hours of stroke onset. A lacune corresponded to the acute stroke could be found in all patients on brain magnetic resonance imaging (MRI), and in 18 (78%) on brain computed tomography (CT). MRI showed additional subclinical or asymptomatic “silent brain infarctions or lacunes” (SBI) in 19 (83%) of 23 patients, and leuko-araiosis (LA) of moderate to severe degree (> grade 2) was present in 61% of patients although dementia was absent. Hypertension is the risk factor in 78% of cases followed by diabetes mellitus, smoking, and elevated plasma cholesterol level. Independence of the types of lacunar syndromes, patients with hypertension and diabetes mellitus are associated with high grade LA. None with normal blood pressure and plasma glucose had grade 3 or grade 4 LA (p < 0.05). In conclusion, evolving-stroke occurs in one- fifth of patients with “first-ever” lacunar infarct within the first 24 hours of stroke onset. SBI was found in 83% of cases. Hypertension and diabetes mellitus are associated with additional SBI and high grade LA. The severity of leuko-araiosis per se dictates the cerebrovascular risks.
基金The Key Research Project of The Third People's Hospital of Hefei,No.SYKZ202301.
文摘BACKGROUND At present,the incidence rate of ischemic stroke in young people is increasing yearly,and the age of onset is increasingly young.Therefore,primary and secondary prevention of ischemic stroke in young people,especially secondary prevention,is particularly crucial.AIM We aimed to comprehensively evaluate risk factors for stroke recurrence in firstever young ischemic stroke(YIS)patients.METHODS The meta-analysis was used to quantitatively analyze the research results on risk factors for stroke recurrence in first-ever YIS patients both domestically and internationally.Stata12.0 software was used for heterogeneity testing,publication bias analysis,sensitivity analysis,and the calculation of combined odds ratios and 95%confidence intervals.RESULTS The odds ratio(OR)values of the relationship between hypertension and hyperlipidemia and recurrence of first-ever YIS were 1.54(1.05-2.26)and 1.12(1.00-1.25),respectively.The OR values of male sex,type 2 diabetes,smoking,drinking and YIS recurrence were 1.66(0.98-2.79),1.01(0.64-1.59),1.21(0.83-1.76),and 1.28(0.82-2.53),respectively.The relationship between male sex,type 2 diabetes,smoking,drinking and YIS recurrence was ambiguous.CONCLUSION Hypertension and hyperlipidemia are important risk factors for stroke recurrence in first-ever YIS patients,and active intervention should be taken.
基金supported by National Natural Science Foundation of China(No.30600511)
文摘Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke. Data collection for this longitudinal study was conducted at baseline through face-toface interviews and follow-up was completed every 3 months via telephone, beginning in 2010 and continuing through 2014. Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior. At baseline, 372 male patients were recruited into the study. Totally, 155(41.7%) of these patients stopped smoking for stroke, and 61(39.3%) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day. Exposure to environmental tobacco smoke at places outside of home and work(such as bars, restaurants)(HR, 2.34; 95% CI, 1.04–5.29, P=0.04), not having a spouse(HR, 0.12; 95% CI, 0.04–0.36; P=0.0002) and smoking at least 20 cigarettes per day before stroke(HR, 2.42; 95% CI, 1.14–5.14, P=0.02) were predictors of smoking relapse. It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke. Environmental tobacco smoke should be addressed by smoke-free policies in public places.
基金This work was supported by the National Natural Science Foundation of China,No.81771250(to XYC)the Natural Science Foundation of Fujian Province of China,Nos.2013J01275(to XYC),2016J01432(to XYC),2018J01255(to XZ)+2 种基金Young and Middle-aged Talents Training Project of Health and Family Planning Committee of Fujian Province,China,No.2015-ZQN-JC-5(to XYC)Joint Funds for the Innovation of Science and Technology of Fujian Province,China,No.2017Y9065(to XYC)High-Level Hospital Foster Grants from Fujian Provincial Hospital,Fujian Province,China,No.2020HSJJ07(to XYC).
文摘Many blood biomarkers are reportedly helpful for predicting post-stroke cognitive impairment(PSCI),but no biomarkers are widely used in clinical practice.The purpose of this study was to investigate the association between the plasma immunoproteasome and patients’90-day prognosis after first-ever acute ischemic stroke.In our prospective,single-center study,259 patients with first-ever acute ischemic stroke were enrolled from the Department of Neurology,Fujian Provincial Hospital,China,from March to September 2014.Of these,27 patients(10.4%)had unfavorable outcomes as assessed by the Modified Rankin Scale(scores of 3–6).The National Institutes of Health Stroke Scale score on admission,plasma N-terminal pro-B-type natriuretic peptide(NT-pro-BNP)levels,and immunopro-teasome subunit(low molecular mass peptide[LMP]2,LMP5,and LMP7)levels were significantly higher in the unfavorable outcome group than in the favorable outcome group.To predict unfavorable outcomes,the optimal cutoff points were National Institutes of Health Stroke Scale score>12,NT-pro-BNP level>1883.5 pg/mL,and LMP2 level>841.4 pg/mL.Of the 193 patients that were able to complete the Mini-Mental State Examination at 90 days poststroke,66 patients(34.2%)had PSCI.Plasma levels of NT-pro-BNP and LMP2 were higher in patients with PSCI than in those without PSCI.To predict PSCI,the optimal cutoff values were age>70.5 years and LMP2 level>630.5 pg/mL.These findings indicate that plasma LMP2 may serve as a new prognostic biomarker of poor outcome and PSCI at 90 days after stroke.This study was approved by the Ethics Committee of Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University(approval No.K2014-01-003)on January 15,2014.
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金This study was funded by the National Natural Science Foundation of China(No.81673273 and No.30600511).
文摘Summary:Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence.However,the relationship between lesion locations and stroke recurrence is unclear.We conducted a prospective cohort study of first-ever ischemic stroke survivors who were consecutively enrolled from January 2010 to December 2015.Stroke recurrence was assessed every 3 months after post-discharge via telephone interviews by trained interviewers.Lesion locations were obtained from hospital-based MRI or CT scans and classified using two classification systems that were based on cerebral hemisphere or vascular territory and brain anatomical structures.Flexible parametric survival models using the proportional hazards scale(PH model)were used to analyze the time-to-event data.Among 633 survivors,63.51%(n-402)had anterior circulation ischemia(ACI),and morc than half of all ACIs occurred in the subcortex.After a median follow-up of 2.5 years,117(18.48%)survivors developed a recurrent stroke.The results of the multivariate PH model showed that survivors with non-brain lesions were at higher risk of recurrence than those with right-side lesions(HR,2.79;95%CI,1.53,5.08;P-0.001).There was no increase in risk among survivors with left-side lesions(HR,0.97;95%CI,0.53,1.75;P=0.914)or both-side lesions(HR,1.24;95%CI,0.75,2.07;P-0.401)compared to those with right-side lesions.Additionally,there were no associations between stroke ecurrence and lesion locations that were classified based on vascular territory and brain anatomical structures.It was concluded that first-ever ischemic stroke survivors with non-brain lesion had higher recurrence risk than those with right-side lesion,although no significant associations were found when the lesion locations were classified by vascular territory and brain anatomical structures.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the National Natural Science Foundation of China,Nos.82272616(to ZL),82271325(to WS)the Natural Science Foundation of Beijing,No.7252076(to YR).
文摘Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of reactive oxygen species in the brain,all of which reflect a dynamic process of change.This complexity hinders achievement of significant therapeutic outcomes with standard stroke treatment procedures,limiting post-stroke recovery.This review presents an innovative post-stroke therapeutic approach that utilizes nanomedicines to modify the cerebral microenvironment.It highlights the primary roles of chronic inflammation and nerve repair issues in causing prolonged impairment in stroke patients.Traditional therapies show limited effectiveness in achieving neuroprotection,immunoregulation,and neural regeneration during the subacute and chronic phases of stroke.Therefore,effective stroke management requires the use of specific therapeutic strategies tailored to the pathological characteristics of each phase.Various types of nanomedicines possess distinct physicochemical properties and can be selected on the basis of the specific therapeutic needs.Surface-modification technologies have significantly enhanced the ability of nanomedicines to penetrate the blood-brain barrier and improve their targeting capabilities in drug administration.However,the stability,biocompatibility,and long-term safety of nanomedicines require further optimization for clinical application.Nanomedicines represent a novel approach to stroke treatment through targeted delivery and multifaceted regulatory mechanisms.These medicines provide distinct advantages,particularly in addressing chronic inflammation and promoting nerve regeneration.As a result,nanomedicines are expected to significantly improve rehabilitation outcomes and quality of life for stroke patients in the future,emerging as a crucial modality for stroke treatment.
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 China Postdoctoral Science Foundation,No.2022M712689the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB1800029+1 种基金The University Student Innovation Project of Yangzhou University,No.XCX20240856The Jiangsu Provincial Science and Technology Talent Project,No.FZ20240964(all to TX).
文摘Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.
基金supported by National Key R&D Program:Key Special Project on Research for the Prevention and Treatment of Common Diseases-2022 Annual Project,Nos.2022YFC2504900,2022YFC2504902(both to ZL).
文摘Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.
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funded by the State Key Laboratory Special Fund(2060204)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2023-I2M-2-001)Strengthen Capacity of Study and Application on the Burden of Disease in Health Care Systems in China:Establishment and Development of Chinese Burden of Disease Research and Dissemination Center(15-208)supported by the China Medical Board(CMB)。
文摘Objective Stroke is the third leading cause of death worldwide,with the highest incidence in Asia,particularly in China,where smoking remains a major risk factor.The smoking prevalence in China is similar to that in Asia.Whether the risk estimates for smoking-related stroke in China and all Asian countries are still unknown which is worth evaluating.Thus,this study aims to compare the Relative Risk(RR)of smoking-attributed stroke among the Chinese and Asian populations.Methods A literature search was conducted from the inception to September 10,2022.Studies meeting the criteria were included.The articles were screened,and related information was extracted.Pooled RRs stratified by smoking status and sex were analyzed,including subgroup analyses for China,other Asian countries,and Asia overall.Finally,publication bias and sensitivity analyses were conducted.Results Thirty-seven articles on the Chinese population and 15 on other Asian populations were included,with a mean Newcastle-Ottawa scale(NOS)score of 7.25.About ever smokers,there had no statistical difference existed in both sexes and females between China and other Asian countries,while the RR of males in other Asian countries[2.31(1.38,3.86)]was higher than that in China[1.21(1.15,1.26)];further subgroup analysis indicated that other Asian countries had higher RR[3.76(3.02,4.67)]in the morbidity subgroup.The RRs of both sexes,males and females,between China and the whole of Asia were not statistically different.As for current and former smokers,no meaningful statistical difference was observed in the pooled RRs of both sexes,males and females,in China,other Asian countries,and all of Asia.Conclusion The RR of males ever smokers in China was smaller than that in other Asian countries due to the few articles of morbidity subgroup,but had no statistical difference with the whole of Asia;other groups of ever smokers,current smokers,and former smokers were not statistically significant with other Asian countries or the whole of Asia.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82192900,82192901,82192904,81390540,and 91846303 to L.L.)the National Key Research and Development Program of China(Grant No.2016YFC0900500 to Y.G.)the Kadoorie Charitable Foundation in Hong Kong,and the Wellcome Trust in the UK(Grant/Award Nos.088158/Z/09/Z,104085/Z/14/Z,and 202922/Z/16/Z to Z.C.).
文摘While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.
