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.

Silent brain infarctions and leuko-araiosis in Chinese patients with first-ever acute lacunar strokes

We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure sensory syndrome (2), ataxic hemiparesis (3), dysarthria clumsy hand syndrome (3), and sensory- motor deficit (5). Nineteen out of the 23 patients presented with completed strokes on arrival to the hospital, and 4 (17%) developed evolving-stroke within 24 hours of stroke onset. A lacune corresponded to the acute stroke could be found in all patients on brain magnetic resonance imaging (MRI), and in 18 (78%) on brain computed tomography (CT). MRI showed additional subclinical or asymptomatic “silent brain infarctions or lacunes” (SBI) in 19 (83%) of 23 patients, and leuko-araiosis (LA) of moderate to severe degree (> grade 2) was present in 61% of patients although dementia was absent. Hypertension is the risk factor in 78% of cases followed by diabetes mellitus, smoking, and elevated plasma cholesterol level. Independence of the types of lacunar syndromes, patients with hypertension and diabetes mellitus are associated with high grade LA. None with normal blood pressure and plasma glucose had grade 3 or grade 4 LA (p < 0.05). In conclusion, evolving-stroke occurs in one- fifth of patients with “first-ever” lacunar infarct within the first 24 hours of stroke onset. SBI was found in 83% of cases. Hypertension and diabetes mellitus are associated with additional SBI and high grade LA. The severity of leuko-araiosis per se dictates the cerebrovascular risks.

A case of paradoxical brain embolism presenting as a typical lacunar stroke

A 59 year old white male presented with a clinical picture typical of lacunar stroke. However, a thorough diagnostic work up showed that the most probable mechanism of stroke was paradoxical brain embolism through a patent foramen ovale. The clinical-neuroradiological mismatch that ultimately lead to the correct interpretation is discussed.

Pure motor stroke as the most frequent lacunar syndrome: A clinical update

Pure motor stroke(PMS), also known as pure motor hemiparesis, is the most common of any lacunar form(between one half and two thirds of cases, depending on the series). In an acute stroke registry, 733 patients presented a lacunar infarct and PMS accounted for 12.7%(n = 342) of all first-ever stroke patients and for 48% of all lacunar syndromes. The posterior limb of the internal capsule, corona radiata, and pons are the most frequent brain topographies. Infarcts in the mesencephalus or medullary pyramid have been exceptionally reported. This present update is focused on the clinical evidence and mechanisms underlying the relationship between PMS and different stroke etiologies.

Florid Autonomic Features Associated with Medullary Lacunar Stroke

Introduction: Autonomic nuclei affection results in variations in hemodynamics, temperature, sweating and ECG. Medullary strokes are challenging in their presentation, bizarre clinical signs, work and neurological outcome. The commonest cause is infarction of the posterior inferior cerebellar artery (PICA). Anatomical areas affected include the inferior cerebellar peduncle, dorsolateral medulla, nuclei of the Trigeminal, vestibular nuclei, Ninth and Vagus nerves. The descending sympathetic tracts and spin thalamic tracts. Serious cardiopulmonary events can complicate 11% of cases. Case Presentation: A middle-aged female developed sub-acute dizziness associated with vomiting and right head pains. She was unable to walk but remained cognitively clear. Her gastrointestinal symptoms were disabling and this was the main factor for presenting to the emergency room. The risk factors included hypertension and diabetes mellitus. Imaging studies were essential for posterior circulation stroke diagnosis and follow-up. She manifested remarkable autonomic features regarding the skin and hemodynamics. Nevertheless, the hospital course was controllable. Discussion: This case report was consistent with relevant literature in the contra lateral vaso motor changes and drop in body temperature during the acute phase. Moreover, our patient developed clinical and radiological extension through double antiplatelets. Superiority of the magnetic resonance imaging (MRI) scans in this patient enabled better diagnostic accuracy in a brainstem stroke. Conclusion: The autonomic features, in this case, represent major symptomatology and clinical signs. The variation in the hemodynamics and persistence of symptoms is thought provoking. This increases the awareness of emergency doctors for acute stroke presenting with autonomic features will enable early detection and helps outcome.

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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.

Convergence of COVID-19 and recurrent stroke:In-hospital mortality risks explored

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.

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.

Early identification of stroke through deep learning with multi-modal human speech and movement data

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.

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.

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.

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.

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.

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.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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.

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.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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.

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.