Objectives:The objective of the study was to explore the impact of auditory stimulation protocol on auditory response in cerebrovascular stroke(CVS)patients.Materials and Methods:A pre-posttest nonequivalent control g...Objectives:The objective of the study was to explore the impact of auditory stimulation protocol on auditory response in cerebrovascular stroke(CVS)patients.Materials and Methods:A pre-posttest nonequivalent control group quasi-experimental study was conducted at Al Mainal Hospital at Al Kars Einy Hospital,Cairo University,among 60 CVS patients,and the sample was randomly assigned through a coin to allocate subjects to study or control group(30 for each group).Auditory stimulation techniques were applied three times per week for the study group for two consecutive weeks.Patients in the control group received only routine hospital care during the study period.The Glasgow Coma Scale(GCS)score for assessing the neurological function and level of arousal and the auditory subscale score of Western Neuro Sensory Stimulation Profile(WNSSP)for assessing auditory response were recorded and compared between the two groups before and after the intervention.Results:There were statistically significant differences between the study group and the control group regarding third reading of GCS score(11.5±0.3 vs.10.6±0.9,t=4.676,P=0.000).The scores of all auditory subscales of WNSSP in the study groups increased after implementing the auditory stimulation protocol(P<0.05).Conclusion:Utilizing the auditory stimulation protocol by nurse proves to be an effective method for enhancing hearing responses in individuals with CVS.展开更多
<strong>Aims:</strong><span style="white-space:normal;font-size:10pt;font-family:;" "=""><strong> </strong>To determine the cardiovascular and cerebrovascula...<strong>Aims:</strong><span style="white-space:normal;font-size:10pt;font-family:;" "=""><strong> </strong>To determine the cardiovascular and cerebrovascular prognosis at 5 years of patients who underwent an ischemic stroke in Senegal. <b>Methods:</b> We performed a descriptive, retrospective and exhaustive study conducted at Principal Hospital of Dakar. We included all patients hospitalized at Principal Hospital of Dakar from 2013 to 201</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">9</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> for an ischemic stroke confirmed by a cerebral CT-Scanner or by magnetic resonance imaging, and who survived the acute phase. <b>Results: </b>Overall, one</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">hundred and seventy-one (171) patients were gathered. Ninety-six (96) male patients account for 56.14% and seventy-five (75) female patients account for 43.86%</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">,</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> with a sex</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">ratio of 1.28. Patients’mean age was 66.33 ±</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""></span><span style="white-space:normal;font-size:10pt;font-family:;" "="">13.99 years. Twenty-one (21) young patients (12.35%), aged less than 50 years, presented with an ischemic stroke. Myocardial infarction was found in a female patient (0</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">.</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">6%) 3 months after she experienced an ischemic stroke, nine (9) patients (5.29%) underwent a recurrence of the ischemic stroke with a mean recurrence period of 8 months and extremes rang</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">ing</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> from 1 to 24 months. Five (5) patients (2.92%) developed dementia with a score less than 28. A 30 years old patient presented with epilepsy 12 months after the ischemic stroke accounting </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">for </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">0.58%. We registered ninety (90) deaths that occurred in a mean period of 24 months ±</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">9.8 after they presented their ischemic stroke, standing for 52.63% amongst which thirty</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">five (35) accounting for 39% were female patients and fifty</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">five patients (55) representing 61% were male patients. Mortality-related factors included: advanced age, past medical history of heart surgery, known </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">as </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">dys</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">lipidemia, physical inactivity, obesity and recurrent ischemic stroke. <b>Conclusion:</b> Long</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">term prognosis of ischemic stroke remains unclear in Senegal. </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">Therefore</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">,</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> a strategy for primary prevention is highly crucial and </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">it </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">requires the control of risk factors in general and that of high blood pressure in particular.</span>展开更多
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
Objective:To evaluate the improvement of dysphagia and the daily amounts of oral fluids served among people who had recently experienced a cerebrovascular stroke(CVS)after applying a nursing intervention protocol.Meth...Objective:To evaluate the improvement of dysphagia and the daily amounts of oral fluids served among people who had recently experienced a cerebrovascular stroke(CVS)after applying a nursing intervention protocol.Methods:A quasi-experimental design was used to examine 60 stroke patients who were randomly and alternatively divided equally into a study group and a control group.Gugging Swallowing Screen(GUSS)and fluid balance chart were used.Within the first 24 h of a patient’s admission,expert nurses were trained in nursing intervention protocol to manage dysphagia and daily oral fluids.Results:Post-nursing intervention,the severity of dysphagia decreased among the study group more than in the control group.Additionally,the study group began taking greater amounts of fluids by the oral route than before the nursing intervention.Conclusions:A standardized nursing intervention protocol is needed to decrease the severity of dysphagia after CVS and increase the amount of daily oral fluids.The presence of a structured theory-based nursing intervention protocol for dysphagia management will greatly contribute to decreasing the consequences of dysphagia after CVS,and can also be expected to attenuate the effects of aspiration pneumonia,dehydration,and malnutrition;further,it also increases adherence to the protocol by both nurses and patients.展开更多
Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in ad...Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in adults, the second leading cause of dementia (after Alzheimer’s disease), and the third leading cause of death (after cancer and cardiovascular disease). It’s also a major cause of depression. The objective of our study was to describe the epidemiological, clinical and evolutionary aspects of stroke in the internal medicine department of Tivaouane Hospital. Material and Method: This is a retrospective study carried out from January 1, 2015 to December 31, 2018 on the files of patients hospitalized for stroke in the medical department of the EPS1 in Tivaouane. We took into account all the patients who had a brain CT (computed tomography) scan. We collected data related to socio-demographic characteristics, history, risk factors, reasons for admission, clinical signs, paraclinical examinations, as well as evolution. Results: Out of 1999 patients, 206 files of patients with stroke were collected, i.e. a proportion of 10.3%. Our study population had a mean age of 65.53 years [16 - 97 years]. We noted a clear predominance of women (50.5%). The majority of the population came from the outskirts of Tivaouane (56.7%). Risk factors for stroke were dominated by hypertension (90.3%), dyslipidemia (19.4%), previous stroke (18.9%), and diabetes (16%). The clinical signs were dominated by a motor deficit (94.1%), speech disorders (67.4%) and consciousness disorders (47%). Ischemic strokes were predominant (65%) over hemorrhagic strokes (34.5%). The outcome was generally unfavorable with 14.6% total recovery, 58.7% recovery with sequelae and a case fatality of 26.7%. Conclusion: It emerges from this study that strokes still remain a real public health problem. Knowledge of populations of risk factors as well as their proper management is fundamental in primary prevention strategies, the only guarantee for a reduction in the still very high morbidity and mortality of this disease.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
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
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
Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofi...Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated tau.However,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological mechanism.An often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and microhemorrhages.Animal models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).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
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
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes ...BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive population.METHODS Between 2013 and 2014,6094 hypertension individuals were included in this,and ischemic stroke cases were documented to the end of 2018.Longitudinal changes of lipid were stratified into four groups:(1)Normal was transformed into normal group;(2)Abnormal was transformed into normal group;(3)Normal was transformed into abnormal group;and(4)Abnormal was transformed into abnormal group.To examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke,we utilized multivariate Cox proportional hazards models with hazard ratio(HR)and 95%CI.RESULTS The average age of the participants was 62.32 years±13.00 years,with 329 women making up 54.0%of the sample.Over the course of a mean follow-up of 4.8 years,143 ischemic strokes happened.When normal was transformed into normal group was used as a reference,after full adjustments,the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group,normal was transformed into abnormal group and abnormal was transformed into abnormal Wei CC et al.Dyslipidemia changed and ischemic stroke WJCC https://www.wjgnet.com 2 February 6,2025 Volume 13 Issue 4 group were 1.089(95%CI:0.598-1.982;P=0.779),2.369(95%CI:1.424-3.941;P<0.001)and 1.448(95%CI:1.002-2.298;P=0.047)(P for trend was 0.233),respectively.CONCLUSION In individuals with hypertension,longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.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
Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.展开更多
BACKGROUND Acute ischemic stroke(AIS)is an abrupt blood flow cessation to a specific brain region within a vascular zone,causing a subsequent decline in neurological capabilities.Stent thrombectomy is a recently estab...BACKGROUND Acute ischemic stroke(AIS)is an abrupt blood flow cessation to a specific brain region within a vascular zone,causing a subsequent decline in neurological capabilities.Stent thrombectomy is a recently established technique for treating AIS.It provides the benefits of being a relatively simple and safe procedure,capable of partially enhancing a patient’s condition.However,some patients may experience endothelial damage and recurrent thrombosis,with clinical outcomes that are not always satisfactory.Hence,the efficacy of this method remains unclear.AIM To survey the association of stent thrombectomy vs standard treatment with neurological function protection,complications,and short-term prognosis in patients diagnosed with AIS.METHODS This study assigned 90 patients with AIS to the observation and control groups(n=45 patients)from December 2020 to December 2022.Stent thrombectomy was conducted in the observation group,whereas routine treatment was provided to the control group.The study assessed the therapeutic outcomes of two groups,including a comparison of their neurological function,living ability,anxiety and depression status,plaque area,serum inflammatory factors,serum Smur100βprotein,neuron-specific enolase(NSE),homocysteine(Hcy),and vascular endo-thelial function.Additionally,the incidence of complications was calculated and analyzed for each group.RESULTS The total effective rate of treatment was 77.78%and 95.56%in the control and observation groups,respectively.After 8 weeks of treatment,the scores on the National Institutes of Health Stroke Scale,Hamilton Anxiety Scale,and Hamilton Depression Scale decreased remarkably;the Barthel index increased remarkably,with better improvement effects of the scores in the observation group(P<0.05);total cholesterol,triglyceride,C-reactive protein,and plaque area lessened remarkably,with fewer patients in the observation group(P<0.05);S-100βprotein,NSE,and Hcy levels lessened remarkably,with fewer patients in the observation group(P<0.05);serum vascular endothelial growth factor and nitric oxide synthase levels increased remarkably,whereas the endothelin-1 level decreased,with better improvement effect in the observation group(P<0.05).Complications occurred in 8.88%of patients in the observation group compared with 33.33%in the control group.CONCLUSION Stent thrombectomy appeared to provide more remarkable neuroprotective effects in patients with AIS compared to the intravenous thrombolysis regimen.Additionally,it has effectively improved the neurological function,daily activities,and vascular endothelial function of patients,while reducing the incidence of complications and improving short-term prognosis.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
To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these me...To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.展开更多
文摘Objectives:The objective of the study was to explore the impact of auditory stimulation protocol on auditory response in cerebrovascular stroke(CVS)patients.Materials and Methods:A pre-posttest nonequivalent control group quasi-experimental study was conducted at Al Mainal Hospital at Al Kars Einy Hospital,Cairo University,among 60 CVS patients,and the sample was randomly assigned through a coin to allocate subjects to study or control group(30 for each group).Auditory stimulation techniques were applied three times per week for the study group for two consecutive weeks.Patients in the control group received only routine hospital care during the study period.The Glasgow Coma Scale(GCS)score for assessing the neurological function and level of arousal and the auditory subscale score of Western Neuro Sensory Stimulation Profile(WNSSP)for assessing auditory response were recorded and compared between the two groups before and after the intervention.Results:There were statistically significant differences between the study group and the control group regarding third reading of GCS score(11.5±0.3 vs.10.6±0.9,t=4.676,P=0.000).The scores of all auditory subscales of WNSSP in the study groups increased after implementing the auditory stimulation protocol(P<0.05).Conclusion:Utilizing the auditory stimulation protocol by nurse proves to be an effective method for enhancing hearing responses in individuals with CVS.
文摘<strong>Aims:</strong><span style="white-space:normal;font-size:10pt;font-family:;" "=""><strong> </strong>To determine the cardiovascular and cerebrovascular prognosis at 5 years of patients who underwent an ischemic stroke in Senegal. <b>Methods:</b> We performed a descriptive, retrospective and exhaustive study conducted at Principal Hospital of Dakar. We included all patients hospitalized at Principal Hospital of Dakar from 2013 to 201</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">9</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> for an ischemic stroke confirmed by a cerebral CT-Scanner or by magnetic resonance imaging, and who survived the acute phase. <b>Results: </b>Overall, one</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">hundred and seventy-one (171) patients were gathered. Ninety-six (96) male patients account for 56.14% and seventy-five (75) female patients account for 43.86%</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">,</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> with a sex</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">ratio of 1.28. Patients’mean age was 66.33 ±</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""></span><span style="white-space:normal;font-size:10pt;font-family:;" "="">13.99 years. Twenty-one (21) young patients (12.35%), aged less than 50 years, presented with an ischemic stroke. Myocardial infarction was found in a female patient (0</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">.</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">6%) 3 months after she experienced an ischemic stroke, nine (9) patients (5.29%) underwent a recurrence of the ischemic stroke with a mean recurrence period of 8 months and extremes rang</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">ing</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> from 1 to 24 months. Five (5) patients (2.92%) developed dementia with a score less than 28. A 30 years old patient presented with epilepsy 12 months after the ischemic stroke accounting </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">for </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">0.58%. We registered ninety (90) deaths that occurred in a mean period of 24 months ±</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">9.8 after they presented their ischemic stroke, standing for 52.63% amongst which thirty</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">five (35) accounting for 39% were female patients and fifty</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">five patients (55) representing 61% were male patients. Mortality-related factors included: advanced age, past medical history of heart surgery, known </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">as </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">dys</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">lipidemia, physical inactivity, obesity and recurrent ischemic stroke. <b>Conclusion:</b> Long</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">-</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">term prognosis of ischemic stroke remains unclear in Senegal. </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">Therefore</span><span style="white-space:normal;font-size:10pt;font-family:;" "="">,</span><span style="white-space:normal;font-size:10pt;font-family:;" "=""> a strategy for primary prevention is highly crucial and </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">it </span><span style="white-space:normal;font-size:10pt;font-family:;" "="">requires the control of risk factors in general and that of high blood pressure in particular.</span>
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Objective:To evaluate the improvement of dysphagia and the daily amounts of oral fluids served among people who had recently experienced a cerebrovascular stroke(CVS)after applying a nursing intervention protocol.Methods:A quasi-experimental design was used to examine 60 stroke patients who were randomly and alternatively divided equally into a study group and a control group.Gugging Swallowing Screen(GUSS)and fluid balance chart were used.Within the first 24 h of a patient’s admission,expert nurses were trained in nursing intervention protocol to manage dysphagia and daily oral fluids.Results:Post-nursing intervention,the severity of dysphagia decreased among the study group more than in the control group.Additionally,the study group began taking greater amounts of fluids by the oral route than before the nursing intervention.Conclusions:A standardized nursing intervention protocol is needed to decrease the severity of dysphagia after CVS and increase the amount of daily oral fluids.The presence of a structured theory-based nursing intervention protocol for dysphagia management will greatly contribute to decreasing the consequences of dysphagia after CVS,and can also be expected to attenuate the effects of aspiration pneumonia,dehydration,and malnutrition;further,it also increases adherence to the protocol by both nurses and patients.
文摘Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in adults, the second leading cause of dementia (after Alzheimer’s disease), and the third leading cause of death (after cancer and cardiovascular disease). It’s also a major cause of depression. The objective of our study was to describe the epidemiological, clinical and evolutionary aspects of stroke in the internal medicine department of Tivaouane Hospital. Material and Method: This is a retrospective study carried out from January 1, 2015 to December 31, 2018 on the files of patients hospitalized for stroke in the medical department of the EPS1 in Tivaouane. We took into account all the patients who had a brain CT (computed tomography) scan. We collected data related to socio-demographic characteristics, history, risk factors, reasons for admission, clinical signs, paraclinical examinations, as well as evolution. Results: Out of 1999 patients, 206 files of patients with stroke were collected, i.e. a proportion of 10.3%. Our study population had a mean age of 65.53 years [16 - 97 years]. We noted a clear predominance of women (50.5%). The majority of the population came from the outskirts of Tivaouane (56.7%). Risk factors for stroke were dominated by hypertension (90.3%), dyslipidemia (19.4%), previous stroke (18.9%), and diabetes (16%). The clinical signs were dominated by a motor deficit (94.1%), speech disorders (67.4%) and consciousness disorders (47%). Ischemic strokes were predominant (65%) over hemorrhagic strokes (34.5%). The outcome was generally unfavorable with 14.6% total recovery, 58.7% recovery with sequelae and a case fatality of 26.7%. Conclusion: It emerges from this study that strokes still remain a real public health problem. Knowledge of populations of risk factors as well as their proper management is fundamental in primary prevention strategies, the only guarantee for a reduction in the still very high morbidity and mortality of this disease.
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 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 National Institute of Health NS104386(to HJA)and AG078245(to HJA).
文摘Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated tau.However,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological mechanism.An often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and microhemorrhages.Animal models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).
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 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.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
文摘BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive population.METHODS Between 2013 and 2014,6094 hypertension individuals were included in this,and ischemic stroke cases were documented to the end of 2018.Longitudinal changes of lipid were stratified into four groups:(1)Normal was transformed into normal group;(2)Abnormal was transformed into normal group;(3)Normal was transformed into abnormal group;and(4)Abnormal was transformed into abnormal group.To examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke,we utilized multivariate Cox proportional hazards models with hazard ratio(HR)and 95%CI.RESULTS The average age of the participants was 62.32 years±13.00 years,with 329 women making up 54.0%of the sample.Over the course of a mean follow-up of 4.8 years,143 ischemic strokes happened.When normal was transformed into normal group was used as a reference,after full adjustments,the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group,normal was transformed into abnormal group and abnormal was transformed into abnormal Wei CC et al.Dyslipidemia changed and ischemic stroke WJCC https://www.wjgnet.com 2 February 6,2025 Volume 13 Issue 4 group were 1.089(95%CI:0.598-1.982;P=0.779),2.369(95%CI:1.424-3.941;P<0.001)and 1.448(95%CI:1.002-2.298;P=0.047)(P for trend was 0.233),respectively.CONCLUSION In individuals with hypertension,longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.
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 NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
文摘BACKGROUND Acute ischemic stroke(AIS)is an abrupt blood flow cessation to a specific brain region within a vascular zone,causing a subsequent decline in neurological capabilities.Stent thrombectomy is a recently established technique for treating AIS.It provides the benefits of being a relatively simple and safe procedure,capable of partially enhancing a patient’s condition.However,some patients may experience endothelial damage and recurrent thrombosis,with clinical outcomes that are not always satisfactory.Hence,the efficacy of this method remains unclear.AIM To survey the association of stent thrombectomy vs standard treatment with neurological function protection,complications,and short-term prognosis in patients diagnosed with AIS.METHODS This study assigned 90 patients with AIS to the observation and control groups(n=45 patients)from December 2020 to December 2022.Stent thrombectomy was conducted in the observation group,whereas routine treatment was provided to the control group.The study assessed the therapeutic outcomes of two groups,including a comparison of their neurological function,living ability,anxiety and depression status,plaque area,serum inflammatory factors,serum Smur100βprotein,neuron-specific enolase(NSE),homocysteine(Hcy),and vascular endo-thelial function.Additionally,the incidence of complications was calculated and analyzed for each group.RESULTS The total effective rate of treatment was 77.78%and 95.56%in the control and observation groups,respectively.After 8 weeks of treatment,the scores on the National Institutes of Health Stroke Scale,Hamilton Anxiety Scale,and Hamilton Depression Scale decreased remarkably;the Barthel index increased remarkably,with better improvement effects of the scores in the observation group(P<0.05);total cholesterol,triglyceride,C-reactive protein,and plaque area lessened remarkably,with fewer patients in the observation group(P<0.05);S-100βprotein,NSE,and Hcy levels lessened remarkably,with fewer patients in the observation group(P<0.05);serum vascular endothelial growth factor and nitric oxide synthase levels increased remarkably,whereas the endothelin-1 level decreased,with better improvement effect in the observation group(P<0.05).Complications occurred in 8.88%of patients in the observation group compared with 33.33%in the control group.CONCLUSION Stent thrombectomy appeared to provide more remarkable neuroprotective effects in patients with AIS compared to the intravenous thrombolysis regimen.Additionally,it has effectively improved the neurological function,daily activities,and vascular endothelial function of patients,while reducing the incidence of complications and improving short-term prognosis.
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 University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.