Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
In this paper, we report the location results for the parent lightning strokes of more than 30 red sprites observed over an asymmetric mesoscale convective system(MCS) on 30 July 2015 in Shandong Province, China, with...In this paper, we report the location results for the parent lightning strokes of more than 30 red sprites observed over an asymmetric mesoscale convective system(MCS) on 30 July 2015 in Shandong Province, China, with a long-baseline lightning location network of very-low-frequency/low-frequency magnetic field sensors. The results show that almost all of these cloud-to-ground(CG) strokes are produced during the mature stage of the MCS, and are predominantly located in the trailing stratiform region, which is similar to analyses of sprite-productive MCSs in North America and Europe. Comparison between the location results for the sprite-producing CG strokes and those provided by the World Wide Lightning Location Network(WWLLN) indicates that the location accuracy of WWLLN for intense CG strokes in Shandong Province is typically within 10 km, which is consistent with the result based on analysis of 2838 sprite-producing CG strokes in the continental United States. Also, we analyze two cases where some minor lightning discharges in the parent flash of sprites can also be located, providing an approach to confine the thundercloud region tapped by the sprite-producing CG strokes.展开更多
In this paper, a novel approach is proposed for denoising of Chinese calligraphy tablet documents. The method includes two phases: First, a partial differential equations (PDE) based the total variation model and Otsu...In this paper, a novel approach is proposed for denoising of Chinese calligraphy tablet documents. The method includes two phases: First, a partial differential equations (PDE) based the total variation model and Otsu thresholding method are used to preprocess the calligraphy document image. Second, a new method based on run-length statistics and structure charac- teristics of Chinese characters is proposed to remove some random and ant-like noises. This includes the optimal threshold se- lection from histogram of run-length probability density, and improved Hough transform algorithm for line shape noise detection and removal. Examples are given in the paper to demonstrate the proposed method.展开更多
Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homoz...Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia,was affected by two occipital ischemic strokes within a period of 5 mo.At the time of the second stroke,while she was being treated with folic acid,acetylsalicylic acid and a gluten-free diet,she had left hemianopsia,left hemiparesthesias,and gait imbalance.Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion,which was extended to the dorsal region of the right thalamus and the ipsilateral thalamocapsular junction.Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present,while antinuclear antibodies,antineuronal antibodies and immune circulating complexes were only slightly elevated.Since the patient was taking folic acid,her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event.A conventional cerebral angiography showed no signs of vasculitis.Finally,rare causes of occipital stroke in young patients,such as Fabry's disease and mitochondrial myopathy,encephalomyopathy,lactic acidosis and stroke-like symptoms,were also excluded by appropriate tests.Thus,the most probable cause for the recurrent strokes in this young woman remained CD,although the mechanisms involved are still unknown.The two main hypotheses concern malabsorption(with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immunemediated mechanisms.CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.展开更多
The importance of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), on the incidence of coronary heart disease (CHD) and stroke are known. However, the importance of blood pressur...The importance of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), on the incidence of coronary heart disease (CHD) and stroke are known. However, the importance of blood pressure (BP)-age shifts regarding the stroke incidence is not clearly known. The BP changes with the advancement of age from the predominance of DBP in the young to the predominance of SBP in the old. This change is due to the stiffening of the large arteries as a result of the aging process and the replacement of the elastic fibers with collagen fibers. This change results in the loss of compliance and the elastic recoil of these vessels leading to increase in pulse wave velocity, central SBP and widening of pulse pressure leading to an increased incidence of CHD and strokes. It has been demonstrated epidemiologically that the SBP rises linearly with age, whereas the DBP rises up to the age of 45-50 years, and then begins to decline after the age of 60 years leading to a progressive widening of PP. Several studies have shown an inverse relationship between DBP and CHD, whereas no such relationship has been demonstrated for stroke. However, a recent study showed an inverse relationship with DBP and stroke when it dropped below 71 mmHg in subjects 50 years of age or older. In contrast, there was a positive association between BP and stroke when both SBP and DBP were ≥ 71 mmHg. These findings suggest that intreating systolic hypertension in the elderly to reduce stroke risk, attention should be paid on the potential harm of low DBP and the widening of PP regarding CHD and stroke. The implications of BP shifts with age and the potential risks of low DBP regarding the risk of stroke will be discussed in this concise review.展开更多
We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure s...We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure sensory syndrome (2), ataxic hemiparesis (3), dysarthria clumsy hand syndrome (3), and sensory- motor deficit (5). Nineteen out of the 23 patients presented with completed strokes on arrival to the hospital, and 4 (17%) developed evolving-stroke within 24 hours of stroke onset. A lacune corresponded to the acute stroke could be found in all patients on brain magnetic resonance imaging (MRI), and in 18 (78%) on brain computed tomography (CT). MRI showed additional subclinical or asymptomatic “silent brain infarctions or lacunes” (SBI) in 19 (83%) of 23 patients, and leuko-araiosis (LA) of moderate to severe degree (> grade 2) was present in 61% of patients although dementia was absent. Hypertension is the risk factor in 78% of cases followed by diabetes mellitus, smoking, and elevated plasma cholesterol level. Independence of the types of lacunar syndromes, patients with hypertension and diabetes mellitus are associated with high grade LA. None with normal blood pressure and plasma glucose had grade 3 or grade 4 LA (p < 0.05). In conclusion, evolving-stroke occurs in one- fifth of patients with “first-ever” lacunar infarct within the first 24 hours of stroke onset. SBI was found in 83% of cases. Hypertension and diabetes mellitus are associated with additional SBI and high grade LA. The severity of leuko-araiosis per se dictates the cerebrovascular risks.展开更多
Co ronavirus disease 2019(COVID-19) has affected a broad demographics,eliciting a more significant effect on specific groups such as males,African Americans,and Hispanic minorities.Treatment of COVID-19 often requires...Co ronavirus disease 2019(COVID-19) has affected a broad demographics,eliciting a more significant effect on specific groups such as males,African Americans,and Hispanic minorities.Treatment of COVID-19 often requires antiviral drugs or monoclonal antibodies.However,immunotherapies such as mesenchymal stem cells and mesenchymal stem cells-derived exosomal vesicles should be evaluated as treatment options for COVID-19.Mesenchymal stem cell thera py offe rs regenerative,anti-inflammatory,and immunomodulato ry properties that can speed up the recovery from COVID-19.Mesenchymal stem cell therapy can also benefit COVID-19 patients who suffer from stro kes,as COVID-19 increases the risk of strokes due to increased cytokines and clotting facto rs.Most stroke cases that occur in COVID-19 patients are ischemic strokes.Therefo re,with the help of mesenchymal stem cell therapy and mesenchymal stem cells-derived exosomes,COVID-19-induced stroke patients might benefit from dual-ended treatment.The o bjective of this review was to discuss COVID-19 and stroke incidence and the available treatment options.展开更多
In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it w...In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it was shown that neutralization of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon alpha (IFN-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), leads to a good therapeutic effect. Anticytokinotherapy is currently used around the world for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, and other Th-1-mediated inflammatory diseases. Pro-inflammatory cytokines have also been found in other conditions (myocardial infarctions, strokes, chronic pain syndromes, etc.). This leads us to believe that hyper- production of pro-inflammatory cytokines forms a basis of a variety of pathological conditions and represents a uniform response of the organism to a wide variety of insults in any part of the body. Thus, we propose to add monoclonal antibodies to (or other blockers of) pro-inflammatory cytokines to the treatment regimens for myocardial infarctions, strokes, and possibly other Th-1-mediated diseases.展开更多
Recurrent strokes are more likely to be disabling or fatal than first ever strokes. The aim of the study is to evaluate transthoracic echocardiographic (TTE) and clinical predictors in patients with first versus those...Recurrent strokes are more likely to be disabling or fatal than first ever strokes. The aim of the study is to evaluate transthoracic echocardiographic (TTE) and clinical predictors in patients with first versus those with recurrent ischemic strokes. A prospective observational comparative study of 217 patients admitted with ischemic strokes who were in sinus rhythm. Two groups of patients were simultaneously enrolled. The first group was 110 patients with first ischemic stroke and the second was 107 patients with recurrent ischemic stroke. TTE was done for all patients. Both echocardiographic and clinical risk factors were compared between both groups. Logistic regression analysis identified predictors for recurrent strokes. Among clinical risk factors hypertension, hyperlipidemia, family history of atherosclerotic vascular disease, prior coronary artery disease, peripheral vascular disease, and chronic kidney disease were significantly higher in recurrent stroke group. Multivariate logistic analysis identified age (OR, 1.03;95% CI, 1.01 - 1.07), hypertension (OR, 2.25;95% CI, 1.03 - 4.92), and hyperlipidemia (OR, 2.73;95% CI, 1.40 - 5.35), as predictors for recurrent ischemic strokes. Left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH) and aortic sclerosis were significantly more common in the recurrent stroke group compared to the first stroke group. However, in multivariate logistic analysis only LVH (OR, 3.50;95% CI, 1.69 - 7.23), was identified as a predictor for recurrent strokes. Older age, hypertension, hyperlipidemia and left ventricular hypertrophy are significant predictors of recurrent ischemic strokes in patients with sinus rhythm. Those patients need more aggressive lipid lowering therapy and optimal blood pressure control.展开更多
Meningitis is a possible complication of pneumococcal infection concerning acute otitis media and sinusitis.It might compromise cognitive function,both for the infection itself and the vascular events that sometimes f...Meningitis is a possible complication of pneumococcal infection concerning acute otitis media and sinusitis.It might compromise cognitive function,both for the infection itself and the vascular events that sometimes follow the acute phase.CASE SUMMARY Here we describe the case of a 32-year-old female patient admitted to the emergency room due to extensive pneumococcal meningitis as a consequence of sinus outbreak.She presented with extensive laminar ischemic damage in the acute phase,resulting in severe cognitive and behavioural impairment.Four years of follow-up,through neuropsychological assessments and neuroradiological investigations,demonstrated the presence of subsequent vascular events,3 months and 2 years after onset.CONCLUSION The case is discussed in light of scientific knowledge of the long-term outcomes of this pathology in order to potentially improve diagnosis and promote better outcomes.展开更多
In this paper, the problem of stroke recognition has been studied, and the strategies and the algorithms related to the problem are proposed or developed. Based on studying some current methods for Chinese characters ...In this paper, the problem of stroke recognition has been studied, and the strategies and the algorithms related to the problem are proposed or developed. Based on studying some current methods for Chinese characters strokes recognition, a new method called combining trial is presented. The analysis and results of experiments showed that the method has the advantage of high degree of steadiness.展开更多
Strokes and cerebral vascular accidents (CVAs) and related disease events are an unfortunate circumstance that inflicts individuals around the world and impacts people every day as individuals and their caregivers. Th...Strokes and cerebral vascular accidents (CVAs) and related disease events are an unfortunate circumstance that inflicts individuals around the world and impacts people every day as individuals and their caregivers. The consequences of these strokes or CVA events are life-changing for all those involved. As a result of long-term disability related to strokes, the caregiver may undergo many emotional, psychological, and physical factors that impact their daily lives. There is a relatively short period of time to react to the necessary change and as a result there may be differences in coping associated with these unexpected health circumstances. Many stoke victims experience motor, cognitive, emotional, and psycho-social deficits and their caregivers may not be prepared for these abrupt life altering effects. The impact for caregivers, factors impacting strokes, and solutions for care will be addressed in the paper. Evidence suggests that post fatigue stroke (PFS) may be triggered by a dysfunction of the stress system. Family caregivers with a low level of social engagement may be more likely to perceived stress, and increased risk for caregiver role strain.展开更多
Background:Fluorescence Microscope is a promising analytical method for the examination of the sequence of strokes of writing inks of different colours,brands,and models in a questioned document.Aims and Objectives:In...Background:Fluorescence Microscope is a promising analytical method for the examination of the sequence of strokes of writing inks of different colours,brands,and models in a questioned document.Aims and Objectives:In the present article,an attempt has been made to categorize the writing inks of different brands and colours on the basis of their fluorescence.Materials and Methods:Atotal of 36 writing inks were used to make the different intersections on a standard A4 sheet which were then analyzed under the excitation filters of the Fluorescence Microscope.Results:The results indicated that the different inks can be characterized optically based on the luminescent components of the ink present in crossed lined intersections.Conclusions:Fluorescence Microscopy is a relatively simple,fast,inexpensive,and non-destructive technology that can be used in conjunction with other,more complex,and expensive technologies to identify the sequence of line crossing.It can provide a novel way of analysis based on the assessment of microelement analysis and the characteristics of diverse ink handwriting samples.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by the National Key Basic Research and Development (973) Program of China (Grant No. 2014CB441405)the Open Research Program of the Key Laboratory of Meteorological Disaster (Nanjing University of Information Science and Technology) of the Ministry of Education (Grant No. KLME1414)+2 种基金the National Natural Science Foundation of China (Grant No. 41574179)the Natural Science Foundation of Excellent Youth Program of China (Grant No. 41622501)“The Hundred Talents Program” of the Chinese Academy of Sciences (Grant No. 2013068)
文摘In this paper, we report the location results for the parent lightning strokes of more than 30 red sprites observed over an asymmetric mesoscale convective system(MCS) on 30 July 2015 in Shandong Province, China, with a long-baseline lightning location network of very-low-frequency/low-frequency magnetic field sensors. The results show that almost all of these cloud-to-ground(CG) strokes are produced during the mature stage of the MCS, and are predominantly located in the trailing stratiform region, which is similar to analyses of sprite-productive MCSs in North America and Europe. Comparison between the location results for the sprite-producing CG strokes and those provided by the World Wide Lightning Location Network(WWLLN) indicates that the location accuracy of WWLLN for intense CG strokes in Shandong Province is typically within 10 km, which is consistent with the result based on analysis of 2838 sprite-producing CG strokes in the continental United States. Also, we analyze two cases where some minor lightning discharges in the parent flash of sprites can also be located, providing an approach to confine the thundercloud region tapped by the sprite-producing CG strokes.
基金Project supported by the National Basic Research Program (973) of China (No. 2002-CB-312101) and the National Natural Science Foundation of China (No. 60773037)
文摘In this paper, a novel approach is proposed for denoising of Chinese calligraphy tablet documents. The method includes two phases: First, a partial differential equations (PDE) based the total variation model and Otsu thresholding method are used to preprocess the calligraphy document image. Second, a new method based on run-length statistics and structure charac- teristics of Chinese characters is proposed to remove some random and ant-like noises. This includes the optimal threshold se- lection from histogram of run-length probability density, and improved Hough transform algorithm for line shape noise detection and removal. Examples are given in the paper to demonstrate the proposed method.
文摘Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia,was affected by two occipital ischemic strokes within a period of 5 mo.At the time of the second stroke,while she was being treated with folic acid,acetylsalicylic acid and a gluten-free diet,she had left hemianopsia,left hemiparesthesias,and gait imbalance.Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion,which was extended to the dorsal region of the right thalamus and the ipsilateral thalamocapsular junction.Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present,while antinuclear antibodies,antineuronal antibodies and immune circulating complexes were only slightly elevated.Since the patient was taking folic acid,her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event.A conventional cerebral angiography showed no signs of vasculitis.Finally,rare causes of occipital stroke in young patients,such as Fabry's disease and mitochondrial myopathy,encephalomyopathy,lactic acidosis and stroke-like symptoms,were also excluded by appropriate tests.Thus,the most probable cause for the recurrent strokes in this young woman remained CD,although the mechanisms involved are still unknown.The two main hypotheses concern malabsorption(with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immunemediated mechanisms.CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.
文摘The importance of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), on the incidence of coronary heart disease (CHD) and stroke are known. However, the importance of blood pressure (BP)-age shifts regarding the stroke incidence is not clearly known. The BP changes with the advancement of age from the predominance of DBP in the young to the predominance of SBP in the old. This change is due to the stiffening of the large arteries as a result of the aging process and the replacement of the elastic fibers with collagen fibers. This change results in the loss of compliance and the elastic recoil of these vessels leading to increase in pulse wave velocity, central SBP and widening of pulse pressure leading to an increased incidence of CHD and strokes. It has been demonstrated epidemiologically that the SBP rises linearly with age, whereas the DBP rises up to the age of 45-50 years, and then begins to decline after the age of 60 years leading to a progressive widening of PP. Several studies have shown an inverse relationship between DBP and CHD, whereas no such relationship has been demonstrated for stroke. However, a recent study showed an inverse relationship with DBP and stroke when it dropped below 71 mmHg in subjects 50 years of age or older. In contrast, there was a positive association between BP and stroke when both SBP and DBP were ≥ 71 mmHg. These findings suggest that intreating systolic hypertension in the elderly to reduce stroke risk, attention should be paid on the potential harm of low DBP and the widening of PP regarding CHD and stroke. The implications of BP shifts with age and the potential risks of low DBP regarding the risk of stroke will be discussed in this concise review.
文摘We report on silent brain infarction (SBI) and leuko- araiosis (LA) of 23 patients with clinically diagnosed “first-ever” acute ischemic lacunar stroke. The lacunar syndromes were pure motor hemiparesis (10), pure sensory syndrome (2), ataxic hemiparesis (3), dysarthria clumsy hand syndrome (3), and sensory- motor deficit (5). Nineteen out of the 23 patients presented with completed strokes on arrival to the hospital, and 4 (17%) developed evolving-stroke within 24 hours of stroke onset. A lacune corresponded to the acute stroke could be found in all patients on brain magnetic resonance imaging (MRI), and in 18 (78%) on brain computed tomography (CT). MRI showed additional subclinical or asymptomatic “silent brain infarctions or lacunes” (SBI) in 19 (83%) of 23 patients, and leuko-araiosis (LA) of moderate to severe degree (> grade 2) was present in 61% of patients although dementia was absent. Hypertension is the risk factor in 78% of cases followed by diabetes mellitus, smoking, and elevated plasma cholesterol level. Independence of the types of lacunar syndromes, patients with hypertension and diabetes mellitus are associated with high grade LA. None with normal blood pressure and plasma glucose had grade 3 or grade 4 LA (p < 0.05). In conclusion, evolving-stroke occurs in one- fifth of patients with “first-ever” lacunar infarct within the first 24 hours of stroke onset. SBI was found in 83% of cases. Hypertension and diabetes mellitus are associated with additional SBI and high grade LA. The severity of leuko-araiosis per se dictates the cerebrovascular risks.
文摘Co ronavirus disease 2019(COVID-19) has affected a broad demographics,eliciting a more significant effect on specific groups such as males,African Americans,and Hispanic minorities.Treatment of COVID-19 often requires antiviral drugs or monoclonal antibodies.However,immunotherapies such as mesenchymal stem cells and mesenchymal stem cells-derived exosomal vesicles should be evaluated as treatment options for COVID-19.Mesenchymal stem cell thera py offe rs regenerative,anti-inflammatory,and immunomodulato ry properties that can speed up the recovery from COVID-19.Mesenchymal stem cell therapy can also benefit COVID-19 patients who suffer from stro kes,as COVID-19 increases the risk of strokes due to increased cytokines and clotting facto rs.Most stroke cases that occur in COVID-19 patients are ischemic strokes.Therefo re,with the help of mesenchymal stem cell therapy and mesenchymal stem cells-derived exosomes,COVID-19-induced stroke patients might benefit from dual-ended treatment.The o bjective of this review was to discuss COVID-19 and stroke incidence and the available treatment options.
文摘In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it was shown that neutralization of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon alpha (IFN-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), leads to a good therapeutic effect. Anticytokinotherapy is currently used around the world for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, and other Th-1-mediated inflammatory diseases. Pro-inflammatory cytokines have also been found in other conditions (myocardial infarctions, strokes, chronic pain syndromes, etc.). This leads us to believe that hyper- production of pro-inflammatory cytokines forms a basis of a variety of pathological conditions and represents a uniform response of the organism to a wide variety of insults in any part of the body. Thus, we propose to add monoclonal antibodies to (or other blockers of) pro-inflammatory cytokines to the treatment regimens for myocardial infarctions, strokes, and possibly other Th-1-mediated diseases.
文摘Recurrent strokes are more likely to be disabling or fatal than first ever strokes. The aim of the study is to evaluate transthoracic echocardiographic (TTE) and clinical predictors in patients with first versus those with recurrent ischemic strokes. A prospective observational comparative study of 217 patients admitted with ischemic strokes who were in sinus rhythm. Two groups of patients were simultaneously enrolled. The first group was 110 patients with first ischemic stroke and the second was 107 patients with recurrent ischemic stroke. TTE was done for all patients. Both echocardiographic and clinical risk factors were compared between both groups. Logistic regression analysis identified predictors for recurrent strokes. Among clinical risk factors hypertension, hyperlipidemia, family history of atherosclerotic vascular disease, prior coronary artery disease, peripheral vascular disease, and chronic kidney disease were significantly higher in recurrent stroke group. Multivariate logistic analysis identified age (OR, 1.03;95% CI, 1.01 - 1.07), hypertension (OR, 2.25;95% CI, 1.03 - 4.92), and hyperlipidemia (OR, 2.73;95% CI, 1.40 - 5.35), as predictors for recurrent ischemic strokes. Left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH) and aortic sclerosis were significantly more common in the recurrent stroke group compared to the first stroke group. However, in multivariate logistic analysis only LVH (OR, 3.50;95% CI, 1.69 - 7.23), was identified as a predictor for recurrent strokes. Older age, hypertension, hyperlipidemia and left ventricular hypertrophy are significant predictors of recurrent ischemic strokes in patients with sinus rhythm. Those patients need more aggressive lipid lowering therapy and optimal blood pressure control.
文摘Meningitis is a possible complication of pneumococcal infection concerning acute otitis media and sinusitis.It might compromise cognitive function,both for the infection itself and the vascular events that sometimes follow the acute phase.CASE SUMMARY Here we describe the case of a 32-year-old female patient admitted to the emergency room due to extensive pneumococcal meningitis as a consequence of sinus outbreak.She presented with extensive laminar ischemic damage in the acute phase,resulting in severe cognitive and behavioural impairment.Four years of follow-up,through neuropsychological assessments and neuroradiological investigations,demonstrated the presence of subsequent vascular events,3 months and 2 years after onset.CONCLUSION The case is discussed in light of scientific knowledge of the long-term outcomes of this pathology in order to potentially improve diagnosis and promote better outcomes.
文摘In this paper, the problem of stroke recognition has been studied, and the strategies and the algorithms related to the problem are proposed or developed. Based on studying some current methods for Chinese characters strokes recognition, a new method called combining trial is presented. The analysis and results of experiments showed that the method has the advantage of high degree of steadiness.
文摘Strokes and cerebral vascular accidents (CVAs) and related disease events are an unfortunate circumstance that inflicts individuals around the world and impacts people every day as individuals and their caregivers. The consequences of these strokes or CVA events are life-changing for all those involved. As a result of long-term disability related to strokes, the caregiver may undergo many emotional, psychological, and physical factors that impact their daily lives. There is a relatively short period of time to react to the necessary change and as a result there may be differences in coping associated with these unexpected health circumstances. Many stoke victims experience motor, cognitive, emotional, and psycho-social deficits and their caregivers may not be prepared for these abrupt life altering effects. The impact for caregivers, factors impacting strokes, and solutions for care will be addressed in the paper. Evidence suggests that post fatigue stroke (PFS) may be triggered by a dysfunction of the stress system. Family caregivers with a low level of social engagement may be more likely to perceived stress, and increased risk for caregiver role strain.
文摘Background:Fluorescence Microscope is a promising analytical method for the examination of the sequence of strokes of writing inks of different colours,brands,and models in a questioned document.Aims and Objectives:In the present article,an attempt has been made to categorize the writing inks of different brands and colours on the basis of their fluorescence.Materials and Methods:Atotal of 36 writing inks were used to make the different intersections on a standard A4 sheet which were then analyzed under the excitation filters of the Fluorescence Microscope.Results:The results indicated that the different inks can be characterized optically based on the luminescent components of the ink present in crossed lined intersections.Conclusions:Fluorescence Microscopy is a relatively simple,fast,inexpensive,and non-destructive technology that can be used in conjunction with other,more complex,and expensive technologies to identify the sequence of line crossing.It can provide a novel way of analysis based on the assessment of microelement analysis and the characteristics of diverse ink handwriting samples.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
