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
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
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
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
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
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
Stroke is the second leading cause of death worldwide and a major cause of disability among adults.With the advancement of medical technology,the survival period of stroke patients has been significantly prolonged,but...Stroke is the second leading cause of death worldwide and a major cause of disability among adults.With the advancement of medical technology,the survival period of stroke patients has been significantly prolonged,but the neuropsychiatric sequelae in the chronic stage have become increasingly prominent.Post-stroke depression is one of the very important manifestations.This article conducts a further discussion on this issue.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
BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and dep...BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroa...Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated ne...Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.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.
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.
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 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 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 Science and Technology Program of Nantong City,No.Key003 and No.JCZ2022040Nantong Young Medical Expert,No.46+2 种基金Science and Technology Program of Nantong Health Committee,No.MA2019003,No.MA2021017,and No.MSZ2024038Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD022,and No.KD2024KYJJZD289Nantong Municipal Health Commission Project,No.MSZ2023020.
文摘Stroke is the second leading cause of death worldwide and a major cause of disability among adults.With the advancement of medical technology,the survival period of stroke patients has been significantly prolonged,but the neuropsychiatric sequelae in the chronic stage have become increasingly prominent.Post-stroke depression is one of the very important manifestations.This article conducts a further discussion on this issue.
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.
文摘BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82174496(to NW),82374574(to NW),82302865(to LL)Shanghai Science and Technology Committee Sailing Program,Nos.23YF1403800(to LL),23YF1405200(to YX)Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance,No.SHDC22023304(to YW).
文摘Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
基金supported by the National Natural Science Foundation of China,specifically through grants(No.8227431382304947)Key Research and Development Project of Shaanxi Province(2023GHZD43).Peer re v iew information。
文摘Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.
