Effects of 8-OHdG,H-FABP and CRP on the Development of Ischemic Cardiomyopathy

[Objectives]To analyze the relationship between serum 8-hydroxydeoxyguanosine(8-OHdG),heart fatty acid-binding protein(H-FABP),C-reactive protein(CRP)levels and clinical efficacy and short-term prognosis in patients with ischemic cardiomyopathy.[Methods]The clinical data of 100 patients with ischemic cardiomyopathy from October 2021 to November 2022 were retrospectively analyzed,and the serum levels of 8-OHdG,H-FABP and CRP were compared before and one week after treatment.The patients were followed up for 12 months after discharge,and the incidence of major adverse cardiovascular events(MACE)was counted during the follow-up period.Univariate and multivariate Logistic regression analysis were used to analyze the prognostic factors of patients with ischemic cardiomyopathy in the near future,and the predictive value of serum 8-OHdG,H-FABP and CRP levels for the prognosis of patients was evaluated by ROC curve.[Results]After 1 week of treatment,the serum levels of 8-OHdG,H-FABP and CRP in patients with ischemic cardiomyopathy were significantly lower than those before treatment(P<0.05).During the follow-up period,34 patients developed MACE;the serum levels of 8-OHdG,H-FABP and CRP in the MACE group were higher than those in the non-MACE group,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that 8-OHdG,H-FABP and CRP were the risk factors of MACE in patients with ischemic cardiomyopathy(P<0.05).ROC curve analysis showed that the combined prediction of 8-OHdG,H-FABP and CRP for MACE in patients with ischemic cardiomyopathy was higher than that of CRP,H-FABP and 8-OHdG alone(P<0.05).[Conclusions]8-OHdG,H-FABP and CRP are closely related to the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy,and the detection of serum 8-OHdG,H-FABP and CRP levels can help to evaluate the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy.

Plasma hemoglobin concentration was related to estimated glomerular filtration rate in elderly patients with ischemic cardiomyopathy

Objectives To study the relationship between plasma hemoglobin concentration and estimated glomerular filtration rate （eGFR） in elderly patients with ischemic cardiomyopathy （ICM）.Methods Clinical data of patients with coronary heart disease who were discharged from The First Affiliated Hospital,Chongqing Medical University between 2005 and 2007 were analyzed retrospectively. Echocardiography results,plasma hemoglobin and creatinine concentration were abstracted from the medical records.The study included 235 Chinese Hart patients with age 60 years and older with angiography confirmed coronary heart disease,silent myocardial ischemia or angina pectoris,of whom 154 had ICM defined as left ventricular end-diastolic diameter （LVDd）,male≥56 mm,female≥51 mm （63. 51±7.70 mm） measured by M-mode echocardiography.The differences in plasma hemoglobin concentration were analyzed retrospec- tively between patients with and without ICM,and between patients with an eGFR【60 ml·min-1·1.73m-2 and those with an eGFR≥60 ml·min-1·1.73m-2.Results There were no significant differences in plasma hemoglobin concentration and eGFR between ICM and non-ICM group (118.49±20.52 g·L-1 vs.115.80±23.32 g·L-1 and 75.13±24.21 ml·min-1·1.73m-2 vs.79.09±28.41 ml·min- 1·1.73m-2,respectively,both P】0.05).However,in both ICM and non-ICM groups,plasma hemoglobin concentration was lower in those with an eGFR【60 ml·min-1·1.73m-2 compared with compared with those with an eGFR≥60 ml·min-1·1.73m-2 group (112. 29±18.61 g·L-1 vs.119.92±20.74L-1,P【0.05);plasma hemoglobin concentration was related positively to eGFR.Conclusions There were no significant changes in plasma hemoglobin concentration and eGFR;however,plasma hemoglobin concentration was related to eGFR significantly positively in elderly patients with ICM due to coronary heart

Endoventricular Spiral Plication for Ischemic Dilated Cardiomyopathy

Surgical ventricular restoration (SVR) procedures have been developed;however, their long-term effectiveness remains controversial. Although a series of endoventricular spiral plication (ESP) has been rarely reported and its long prognosis is still unknown;this method has a unique concept of left ventricular (LV) restoration without artificial patch materials. Here, we describe the case of a patient with ischemic cardiomyopathy and ischemic mitral regurgitation who successfully underwent ESP, mitral valve repair, and coronary artery bypass grafting. ESP was effective in papillary muscle approximation for avoiding heart failure;however, the noted improvement of LV wall thickening might be temporary.

Hypoglycemic myocardial stunning as cause of cardiogenic shock in a patient with ischemic cardiomyopathy: A case report and review of literature

Hypoglycemia is a common complication seen in patients with diabetes mellitus and has been proven to have adverse effects on cardiovascular mortality. Hypoglycemia can potentially lead to worsening of cardiac function in patients with ischemic heart disease. We present a case of cardiogenic shock in a patient with hypoglycemia secondary to insulin accumulation due to worsening renal function with dramatic recovery of shock once his sugars normalized.

Analysis about the effect of trimetazidine combined with atorvastation calcium on myocardin i level, cardiac and renal function in patients with ischemic cardiomyopathy

Objective:Analyze the effect of trimetazidine combined with atorvastation calcium on Myocardin I level, cardiac and renal function in patients with Ischemic cardiomyopathy. Methods:A total of 82 patients who were admitted in our hospital from January 2013 to May 2016 were selected and divided them randomly into the research group and the control group. All subjects were treated with conventional therapy after admission. On this basis, the control group was given atorvastation calcium, meanwhile the research group was given trimetazidine combined with atorvastation calcium. Then analyzed the cTnI level, evaluated their cardiac and renal function (cardiac function indexes: LVEF, LVESD, LVEDD, renal function indexes: Scr, BUN and mALB) after three months treatment.Results: After treatment, the level of cTnI, LVESD and LVEDD in this two groups were decreased dramatically, the level of cTnI, LVESD and LVEDD in the research group were (0.51±0.24) ng/mL, (38.35±3.94) mm and (51.43±4.56) mm respectively, compared with the control group, these levels were significantly decreased;the level of LVEF was (51.10±4.07)% in research group, increased more obviously than the control group, and the difference was statistical significant. The Scr, BUN and mALB in two groups were decreased after treatment, the research group was significantly reduced, in addition, these levels in research group were (80.14±10.21) μmol/L, (5.89±1.06) mmol/L and (51.35±20.94) mg/24 h respectively, lower than the control group.Conclusion: The therapy of trimetazidine combined with atorvastation calcium in patients with Ischemic cardiomyopathy, was worthy of clinical application, seeing that can ameliorate effectively myocardial injury , the cardiac and renal function.

Effect of Danhong injection on neuroendocrine molecules and ventricular remodeling in patients with ischemic cardiomyopathy heart failure

Objective:To study the effect of Danhong injection on neuroendocrine molecules and ventricular remodeling in patients with ischemic cardiomyopathy heart failure.Methods: 80 cases of patients with ischemic cardiomyopathy heart failure who were treated in our hospital between March 2014 and December 2016 were collected and divided into control group (n=40) and observation group (n=40) according to random number table. The control group received regular treatment, the observation group received regular + Danhong injection treatment, and both therapies lasted for 14 d a course, two sessions. Serum contents of neuroendocrine molecules and ventricular remodeling-related indexes, Doppler ultrasonic ventricular remodeling parameter levels, and so on were compared between two groups of patients before and after treatment.Results: Before treatment, serum contents of neuroendocrine molecules and ventricular remodeling-related indexes as well as Doppler ultrasonic ventricular remodeling parameter levels were not statistically different between two groups of patients. After treatment, serum neuroendocrine molecules NT-proBNP, ANP, AngⅡ, ALD and NE contents of observation group were lower than those of control group, serum ventricular remodeling indexes TGF-β1, NF-κB, CysC and FGF23 contents were lower than those of control group, and ultrasonic ventricular remodeling parameters LVMI, LVRI, RVEDV and RVESV levels were lower than those of control group.Conclusion: Adjuvant Danhong injection therapy helps optimize the neuroendocrine molecule contents and inhibit the ventricular remodeling process in patients with ischemic cardiomyopathy heart failure.

Arrhythmic risk stratification in ischemic,non-ischemic and hypertrophic cardiomyopathy:A two-step multifactorial,electrophysiology study inclusive approach

Annual arrhythmic sudden cardiac death ranges from 0.6%to 4%in ischemic cardiomyopathy(ICM),1%to 2%in non-ischemic cardiomyopathy(NICM),and 1%in hypertrophic cardiomyopathy(HCM).Towards a more effective arrhythmic risk stratification(ARS)we hereby present a two-step ARS with the usage of seven non-invasive risk factors:Late potentials presence(≥2/3 positive criteria),premature ventricular contractions(≥30/h),non-sustained ventricular tachycardia(≥1episode/24 h),abnormal heart rate turbulence(onset≥0%and slope≤2.5 ms)and reduced deceleration capacity(≤4.5 ms),abnormal T wave alternans(≥65μV),decreased heart rate variability(SDNN<70ms),and prolonged QT_(c)interval(>440 ms in males and>450 ms in females)which reflect the arrhythmogenic mechanisms for the selection of the intermediate arrhythmic risk patients in the first step.In the second step,these intermediate-risk patients undergo a programmed ventricular stimulation(PVS)for the detection of inducible,truly high-risk ICM and NICM patients,who will benefit from an implantable cardioverter defibrillator.For HCM patients,we also suggest the incorporation of the PVS either for the low HCM Risk-score patients or for the patients with one traditional risk factor in order to improve the inadequate sensitivity of the former and the low specificity of the latter.

Experimental Study of a New Operative Procedure for Non -Ischemic Dilated Cardiomyopathy - Overlapping Cardiac Volume Reduction Operation

Objectives To assess a newly devised procedure of cardiac volume reduction without resection of cardiac muscle and evaluated in experimental settings. Methods Ten beagle dogs underwent a rapid pacing leading to heart failure for 3 weeks and received the left ventricular reduction termed overlapping cardiac volume reduction operation (OLCVR) , which consisted of a longitudinal incision in left ventricular (LV) free wall, sutures of the left marginal to the septal wall, and the right marginal to LV free wall. A slope of the linear preload recruitable stroke work relationship ( Mw), with a X - intercept (Vo) were calculated as the precise indicators of left ventricular systolic function. The constant of isovolumic pressure decay (Tau) and a peak filling rate (PFR) were also calculated as the indicators of LV diastolic function. Results LV end- diastolic dimensions was significantly reduced by OLCVR (43 ± 2 to 25 ± 1 ; mm). Fractional shortening was significantly improved by OLCVR (11 ±2 to 30±4;% ). Mw (erg cm^(-3) * 10~3) was also significantly improved (21±2 to 33±3 (p < 0. 001 ) ), whereas Vo, Tau and PFR did not show significant changes. Conclusions The OLCVR significantly increased in the early LV systolic function without detrimental effects on diastolic function. This procedure may become a therapeutic option for end - stage cardiomyopathy.

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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.

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

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.

Relationship between longitudinal changes in lipid composition and ischemic stroke among hypertensive patients

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.

Cell polarization in ischemic stroke: molecular mechanisms and advances

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.

Exosomes:the next-generation therapeutic platform for ischemic stroke

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.

Association of stent thrombectomy and conventional treatment with neuroprotection, complications, anxiety, and depression in acute ischemic stroke patients

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.

PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

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.

Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke

Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.