Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Following an acute stroke,patients often encounter a range of impairments affecting their physical,cognitive,verbal,and social capabilities.Poststroke depression(PSD)has been identified as a significant consequence of...Following an acute stroke,patients often encounter a range of impairments affecting their physical,cognitive,verbal,and social capabilities.Poststroke depression(PSD)has been identified as a significant consequence of stroke and serves as a crucial predictor of patient outcomes.The diagnosis of PSD presents a challenge,as the physical manifestations following a stroke can overlap with certain depressive symptoms,leading to a potential underdiagnosis of this condition.This review employs a narrative approach to synthesize diverse findings within this domain.PSD is categorized as an organic mood disorder,and a more accurate diagnosis may be achieved by considering the location of the stroke,the patient's specific symptoms,and the timeline of depressive symptom onset.Notably,if depressive symptoms emerge at more than one year poststroke,the likelihood of PSD diminishes.The etiology of PSD is currently understood to stem from a combination of physiological and psychosocial factors,as well as their interactions.Several mechanisms associated with PSD have been identified,including inflammation,dysregulation of the hypothalamic-pituitary-adrenal axis,oxidative stress,autophagy,apoptosis,abnormal neurotrophic responses,glutamate-mediated excitotoxicity,dysfunction within brain networks,reduced monoamine levels,locations of brain lesions,and psychosocial influences.This review also outlines potential directions for future research.展开更多
Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In t...Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.展开更多
BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and familie...BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and families.By integrating patient information across these three domains,it facilitates the delivery of tailored guidance,health risk assessments,and three-in-one health education.AIM To explore the effects of the HCH-CHM model on stroke risk reduction in highrisk populations.METHODS In total,110 high-risk stroke patients screened in the community from January 2019 to January 2023 were enrolled,with 52 patients in the control group receiving routine health education and 58 in the observation group receiving HCH-CHM model interventions based on routine health education.Stroke awareness scores,health behavior levels,medication adherence,blood pressure,serum biochemical markers(systolic/diastolic blood pressure,total cholesterol,and triglyceride),and psychological measures(self-rating anxiety/depression scale)were evaluated and compared between groups.RESULTS The observation group showed statistically significant improvements in stroke awareness scores and health behavior levels compared to the control group(P<0.05),with notable enhancements in lifestyle and dietary habits(P<0.05)and reductions in postintervention systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,self-rating anxiety scale,and self-rating depression scale scores(P<0.05).CONCLUSION The HCH-CHM model had a significant positive effect on high-risk stroke populations,effectively increasing disease awareness,improving health behavior and medication adherence,and appropriately ameliorating blood pressure,serum biochemical marker levels,and negative psychological symptoms.展开更多
Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to...Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.展开更多
Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores th...Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.展开更多
This editorial comments on the article by Desai et al,which investigates the impact of coronavirus disease 2019(COVID-19)on in-hospital mortality among patients with recurrent stroke using data from the 2020 National ...This editorial comments on the article by Desai et al,which investigates the impact of coronavirus disease 2019(COVID-19)on in-hospital mortality among patients with recurrent stroke using data from the 2020 National Inpatient Sample.The findings reveal significantly higher mortality rates in COVID-19-positive patients compared to non-COVID-19 patients,particularly among middle-aged individuals,males,and ethnic minorities.This editorial explores the underlying mechanisms contributing to these outcomes and discusses the clinical implications for targeted management strategies in high-risk groups.The results emphasize the need for comprehensive approaches to mitigate the heightened risks faced by recurrent stroke patients during the COVID-19 pandemic.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
Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective dat...Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective data processing for diagnosis and treatment of different diseases including stroke.This technology has vastly improved the patient classification based on their predicted stroke outcome.It helps in quicker decision-making,improves diagnosis precision,and enhances patient care.ML techniques have occasionally been applied extensively to address complex issues related to stroke such as the prediction of stroke prevalence at an early stage.The ability of deep learning(DL)algorithms,a crucial element of AI,is becoming popular in stroke imaging analysis because it automatically extracts features without requiring domain expertise.In the preclinical setup for stroke studies,ML/DL models are commendably used for the detection of vascular thrombi,stroke core,and penumbra size,to identify artery occlusion,compute perfusion maps,detect intracranial hemorrhage(ICH),prediction of infarct,assessing the severity of hemorrhagic transformation,and forecasting patient outcomes.The robust automatic data processing,excellent generalization,self-learning,and precise decision-making abilities of such models have contributed immensely to the advancement of stroke therapy.In the preclinical setup,the time-investing behavioral studies of the animals are also effectively analyzed by AI based algorithms.Understanding the algorithms and models based on AI is yet to be simplified for its appli-cation in stroke therapy in present clinical settings,thus,in the present review attempts have been made to present it in a simplified manner to facilitate translation.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
Objective The relationship between fish consumption and stroke is inconsistent,and it is uncertain whether this association varies across predicted stroke risks.Methods A cohort study comprising 95,800 participants fr...Objective The relationship between fish consumption and stroke is inconsistent,and it is uncertain whether this association varies across predicted stroke risks.Methods A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted.A standardized questionnaire was used to collect data on fish consumption.Participants were stratified into low-and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores.Hazard ratios(HRs)and 95%confidence intervals(CIs)were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction(RERI),attributable proportion(AP),and synergy index(SI).Results During 703,869 person-years of follow-up,2,773 incident stroke events were identified.Higher fish consumption was associated with a lower risk of stroke,particularly among moderate-to-high-risk individuals(HR=0.53,95%CI:0.47-0.60)than among low-risk individuals(HR=0.64,95%CI:0.49-0.85).A significant additive interaction between fish consumption and predicted stroke risk was observed(RERI=4.08,95%CI:2.80-5.36;SI=1.64,95%CI:1.42-1.89;AP=0.36,95%CI:0.28-0.43).Conclusion Higher fish consumption was associated with a lower risk of stroke,and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.展开更多
BACKGROUND Post-stroke depression(PSD),a condition commonly developed in patients with chronic stroke,impairs both functional rehabilitation and daily living.AIM To comprehensively analyze PSD contributors in chronic ...BACKGROUND Post-stroke depression(PSD),a condition commonly developed in patients with chronic stroke,impairs both functional rehabilitation and daily living.AIM To comprehensively analyze PSD contributors in chronic phase stroke and construct a precise nomogram.METHODS Two hundred patients with chronic stroke admitted in over 7 years(January 2017 to January 2024),were enrolled and categorized into the PSD group(n=96)and the non-PSD(NPSD)group(n=104).Demographic characteristics,clinicopathological data,and biochemical indicators were collected and analyzed by univariate analysis.Significant predictors identified in the univariate analysis were subsequently incorporated into a binary logistic regression model to assess their independent effects on PSD risk.The discriminative ability/calibration of the developed PSD prediction nomogram was assessed.RESULTS Compared with the NPSD group,the PSD group included a higher proportion of patients aged≥60 years,divorced/widowed,with an education level below senior high school,presenting with≥2 comorbidities,exhibiting severe neurological impairment,and having multiple lesions.Additionally,the PSD group showed significantly higher neutrophil-to-lymphocyte ratio(NLR)and platelet-tolymphocyte ratio(PLR)than the NPSD group.After assigning values to significant predictors,multivariate analysis indicated that educational level(P=0.046),NLR(P<0.001),and PLR(P<0.001)were independently associated with PSD in patients with chronic stroke.The developed nomogram exhibited favorable discrimination performance.The nomogram's calibration remained accurate for high-risk stratification but displayed modest inconsistencies in lowand middle-risk categories.CONCLUSION Education level,NLR,and PLR independently contribute to PSD in patients with chronic stroke.The constructed nomogram effectively predicts PSD risk within the range of 0.10-0.90,presenting a valuable tool for clinical monitoring and risk assessment of PSD in patients with chronic stroke.展开更多
Post-stroke depression(PSD)is a prevalent but often underdiagnosed complication affecting stroke survivors,with significant implications for recovery and quality of life.Emerging evidence suggests that central obesity...Post-stroke depression(PSD)is a prevalent but often underdiagnosed complication affecting stroke survivors,with significant implications for recovery and quality of life.Emerging evidence suggests that central obesity,as measured by the weight-to-waist index(WWI),may play a crucial role in PSD risk and severity.Traditional obesity metrics,such as body mass index,may not accurately capture the impact of visceral fat distribution on neuropsychiatric outcomes.This letter highlights the growing recognition of WWI as a precise indicator of metabolic and inflammatory disturbances linked to post-stroke mental health.Integrating WWI into routine stroke rehabilitation assessments could facilitate early identification of high-risk patients and improve intervention strategies.Further research is needed to establish standardized WWI cutoff values and explore potential therapeutic targets for PSD prevention.展开更多
The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first i...The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.展开更多
Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modu...Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.展开更多
Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are...Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.展开更多
Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing a...It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
文摘Following an acute stroke,patients often encounter a range of impairments affecting their physical,cognitive,verbal,and social capabilities.Poststroke depression(PSD)has been identified as a significant consequence of stroke and serves as a crucial predictor of patient outcomes.The diagnosis of PSD presents a challenge,as the physical manifestations following a stroke can overlap with certain depressive symptoms,leading to a potential underdiagnosis of this condition.This review employs a narrative approach to synthesize diverse findings within this domain.PSD is categorized as an organic mood disorder,and a more accurate diagnosis may be achieved by considering the location of the stroke,the patient's specific symptoms,and the timeline of depressive symptom onset.Notably,if depressive symptoms emerge at more than one year poststroke,the likelihood of PSD diminishes.The etiology of PSD is currently understood to stem from a combination of physiological and psychosocial factors,as well as their interactions.Several mechanisms associated with PSD have been identified,including inflammation,dysregulation of the hypothalamic-pituitary-adrenal axis,oxidative stress,autophagy,apoptosis,abnormal neurotrophic responses,glutamate-mediated excitotoxicity,dysfunction within brain networks,reduced monoamine levels,locations of brain lesions,and psychosocial influences.This review also outlines potential directions for future research.
基金supported by Shanghai Shenkang Center Demonstration Research Ward Construction,No.SHDC2022CRW010(to MF)Shanghai Shenkang Center Medical Enterprise Integration and Innovation Collaborative Special Project,No.SHDC2022CRT018(to MF)+4 种基金Shanghai Health System Key Supported Discipline-Rehabilitation Medicine,No.2023ZDFC0301(to JT)Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine,No.23KFL009(to JT)Shanghai Postdoctoral Excellence Program,No.2022515(to CY)Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan,No.23YF1447600(to CY)China Postdoctoral Science Foundation,No.2023M732338(to CY).
文摘Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.
基金Supported by Guiding Project of Hebei Provincial Health Commission,No.20201190 and 20180220.
文摘BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and families.By integrating patient information across these three domains,it facilitates the delivery of tailored guidance,health risk assessments,and three-in-one health education.AIM To explore the effects of the HCH-CHM model on stroke risk reduction in highrisk populations.METHODS In total,110 high-risk stroke patients screened in the community from January 2019 to January 2023 were enrolled,with 52 patients in the control group receiving routine health education and 58 in the observation group receiving HCH-CHM model interventions based on routine health education.Stroke awareness scores,health behavior levels,medication adherence,blood pressure,serum biochemical markers(systolic/diastolic blood pressure,total cholesterol,and triglyceride),and psychological measures(self-rating anxiety/depression scale)were evaluated and compared between groups.RESULTS The observation group showed statistically significant improvements in stroke awareness scores and health behavior levels compared to the control group(P<0.05),with notable enhancements in lifestyle and dietary habits(P<0.05)and reductions in postintervention systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,self-rating anxiety scale,and self-rating depression scale scores(P<0.05).CONCLUSION The HCH-CHM model had a significant positive effect on high-risk stroke populations,effectively increasing disease awareness,improving health behavior and medication adherence,and appropriately ameliorating blood pressure,serum biochemical marker levels,and negative psychological symptoms.
基金supported by the Scientific Research Project of China Rehabilitation Research Center,No.2021zx-23the National Natural Science Foundation of China,No.32100925the Beijing Nova Program,No.Z211100002121038。
文摘Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.
文摘Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.
文摘This editorial comments on the article by Desai et al,which investigates the impact of coronavirus disease 2019(COVID-19)on in-hospital mortality among patients with recurrent stroke using data from the 2020 National Inpatient Sample.The findings reveal significantly higher mortality rates in COVID-19-positive patients compared to non-COVID-19 patients,particularly among middle-aged individuals,males,and ethnic minorities.This editorial explores the underlying mechanisms contributing to these outcomes and discusses the clinical implications for targeted management strategies in high-risk groups.The results emphasize the need for comprehensive approaches to mitigate the heightened risks faced by recurrent stroke patients during the COVID-19 pandemic.
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Department of Pharmaceuticals Ministry of Chemicals and Fertilizer,Government of India and National Institute of Pharmaceutical Education and Research(NIPER)Ahmedabad,Gandhinagar,India。
文摘Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective data processing for diagnosis and treatment of different diseases including stroke.This technology has vastly improved the patient classification based on their predicted stroke outcome.It helps in quicker decision-making,improves diagnosis precision,and enhances patient care.ML techniques have occasionally been applied extensively to address complex issues related to stroke such as the prediction of stroke prevalence at an early stage.The ability of deep learning(DL)algorithms,a crucial element of AI,is becoming popular in stroke imaging analysis because it automatically extracts features without requiring domain expertise.In the preclinical setup for stroke studies,ML/DL models are commendably used for the detection of vascular thrombi,stroke core,and penumbra size,to identify artery occlusion,compute perfusion maps,detect intracranial hemorrhage(ICH),prediction of infarct,assessing the severity of hemorrhagic transformation,and forecasting patient outcomes.The robust automatic data processing,excellent generalization,self-learning,and precise decision-making abilities of such models have contributed immensely to the advancement of stroke therapy.In the preclinical setup,the time-investing behavioral studies of the animals are also effectively analyzed by AI based algorithms.Understanding the algorithms and models based on AI is yet to be simplified for its appli-cation in stroke therapy in present clinical settings,thus,in the present review attempts have been made to present it in a simplified manner to facilitate translation.
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 the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003,and 2017-I2M-1-004)the National High Level Hospital Clinical Research Funding(2022-GSPGG-1,2022-GSP-GG-2)+2 种基金the Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers,CAMS(2019RU038)the National Key Research and Development Program of China(2018YFE0115300 and 2017YFC0211700)the National Natural Science Foundation of China(82030102,12126602).
文摘Objective The relationship between fish consumption and stroke is inconsistent,and it is uncertain whether this association varies across predicted stroke risks.Methods A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted.A standardized questionnaire was used to collect data on fish consumption.Participants were stratified into low-and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores.Hazard ratios(HRs)and 95%confidence intervals(CIs)were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction(RERI),attributable proportion(AP),and synergy index(SI).Results During 703,869 person-years of follow-up,2,773 incident stroke events were identified.Higher fish consumption was associated with a lower risk of stroke,particularly among moderate-to-high-risk individuals(HR=0.53,95%CI:0.47-0.60)than among low-risk individuals(HR=0.64,95%CI:0.49-0.85).A significant additive interaction between fish consumption and predicted stroke risk was observed(RERI=4.08,95%CI:2.80-5.36;SI=1.64,95%CI:1.42-1.89;AP=0.36,95%CI:0.28-0.43).Conclusion Higher fish consumption was associated with a lower risk of stroke,and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
文摘BACKGROUND Post-stroke depression(PSD),a condition commonly developed in patients with chronic stroke,impairs both functional rehabilitation and daily living.AIM To comprehensively analyze PSD contributors in chronic phase stroke and construct a precise nomogram.METHODS Two hundred patients with chronic stroke admitted in over 7 years(January 2017 to January 2024),were enrolled and categorized into the PSD group(n=96)and the non-PSD(NPSD)group(n=104).Demographic characteristics,clinicopathological data,and biochemical indicators were collected and analyzed by univariate analysis.Significant predictors identified in the univariate analysis were subsequently incorporated into a binary logistic regression model to assess their independent effects on PSD risk.The discriminative ability/calibration of the developed PSD prediction nomogram was assessed.RESULTS Compared with the NPSD group,the PSD group included a higher proportion of patients aged≥60 years,divorced/widowed,with an education level below senior high school,presenting with≥2 comorbidities,exhibiting severe neurological impairment,and having multiple lesions.Additionally,the PSD group showed significantly higher neutrophil-to-lymphocyte ratio(NLR)and platelet-tolymphocyte ratio(PLR)than the NPSD group.After assigning values to significant predictors,multivariate analysis indicated that educational level(P=0.046),NLR(P<0.001),and PLR(P<0.001)were independently associated with PSD in patients with chronic stroke.The developed nomogram exhibited favorable discrimination performance.The nomogram's calibration remained accurate for high-risk stratification but displayed modest inconsistencies in lowand middle-risk categories.CONCLUSION Education level,NLR,and PLR independently contribute to PSD in patients with chronic stroke.The constructed nomogram effectively predicts PSD risk within the range of 0.10-0.90,presenting a valuable tool for clinical monitoring and risk assessment of PSD in patients with chronic stroke.
基金The New Professor Research Program of Korean Technology in 2025.
文摘Post-stroke depression(PSD)is a prevalent but often underdiagnosed complication affecting stroke survivors,with significant implications for recovery and quality of life.Emerging evidence suggests that central obesity,as measured by the weight-to-waist index(WWI),may play a crucial role in PSD risk and severity.Traditional obesity metrics,such as body mass index,may not accurately capture the impact of visceral fat distribution on neuropsychiatric outcomes.This letter highlights the growing recognition of WWI as a precise indicator of metabolic and inflammatory disturbances linked to post-stroke mental health.Integrating WWI into routine stroke rehabilitation assessments could facilitate early identification of high-risk patients and improve intervention strategies.Further research is needed to establish standardized WWI cutoff values and explore potential therapeutic targets for PSD prevention.
基金supported by the National Natural Science Foundation of China,Nos.82104560(to CL),U21A20400(to QW)the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,No.2022-JYB-JBZR-004(to XW)。
文摘The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.
基金supported by the National Natural Science Foundation of China, Nos.82201474 (to GL), 82071330 (to ZT), and 92148206 (to ZT)Key Research and Discovery Program of Hubei Province, No.2021BCA109 (to ZT)。
文摘Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.
基金supported by the Ministry of Science and Technology of China,No.2020AAA0109605(to XL)Meizhou Major Scientific and Technological Innovation PlatformsProjects of Guangdong Provincial Science & Technology Plan Projects,No.2019A0102005(to HW).
文摘Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the National Natural Science Foundation of China,Nos.82274313(to YD),82204746(to ML),82003982(to TL).
文摘It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
