Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This articl...Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This article outlines its objectives,operational structure,patient population,quality improvement(QI)intervention tools,data elements,data collection methodology and current patient and hospital data.Methods The CSCA is a national,hospital-based,multicentre,voluntary,multifaceted intervention and continuous QI initiative.This multifaceted intervention includes stroke centre development,written care protocols,workshops and a monitoring/feedback system of evidencebased performance measures.The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital.results As of July 2017,1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433264 patients with acute stroke/transient ischaemic attacks(TIA),including 352572(81.38%)acute ischaemic stroke,30362(7.01%)TIA,42080(9.71%)spontaneous intracranial haemorrhage,5505(1.27%)subarachnoid haemorrhage and 2745(0.63%)not specified stroke.Conclusion The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and,ultimately,improve patient outcomes.It supports the CSA mission to reduce stroke burden in China.展开更多
Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia.However,con-ventional bulk sequencing makes it challenging to depict th...Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia.However,con-ventional bulk sequencing makes it challenging to depict this complex immune network.Using single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune cells.Microglia were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal regeneration.Trajectory inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated MDMs.Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying mechanisms.This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.展开更多
目的构建基于MRI扩散加权成像(diffusion-weighted imaging,DWI)的深度学习模型,讨论其对急性缺血性卒中静脉溶栓治疗患者90天预后的预测价值。材料与方法回顾性分析了2家医院进行静脉溶栓治疗的677名急性缺血性卒中(acute ischemic str...目的构建基于MRI扩散加权成像(diffusion-weighted imaging,DWI)的深度学习模型,讨论其对急性缺血性卒中静脉溶栓治疗患者90天预后的预测价值。材料与方法回顾性分析了2家医院进行静脉溶栓治疗的677名急性缺血性卒中(acute ischemic stroke,AIS)患者的临床及影像学资料,通过影像储存和传输系统(picture archiving and communication systems,PACS)收集患者MRI-DWI图像,使用深度神经网络提取患者图像特征。我们将数据集1(医院1)随机分为训练集(70%)和测试集(30%),建立基于临床特征(模型A)和MRI-DWI影像组学特征(模型B)的传统机器学习模型,基于MRI-DWI深度学习特征的深度学习模型(模型C)以及结合临床特征和深度学习特征的组合模型(模型D),预测AIS患者接受静脉溶栓治疗后90天预后[通过评估改良Rankin评分(modified Rankin Scale,mRS),评分<2分表示预后良好]。数据集2(医院2)用于外部验证。通过受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under the curve,AUC)评估模型的预测性能。为了比较不同模型的AUC值差异是否有统计学意义,进一步采用DeLong检验进行统计分析,评估各模型之间AUC差异的显著性。结果基于临床特征和DWI-MRI影像组学特征的机器学习模型A和模型B以及深度学习模型C的AUC分别为0.705[95%置信区间(confidence interval,CI):0.613~0.792]、0.846(95%CI:0.777~0.906)和0.877(95%CI:0.811~0.934)。结合临床和深度学习特征的组合模型D在预测AIS患者静脉溶栓后90天预后方面表现出显著优势,其AUC值为0.930(95%CI:0.890~0.963)。此外,深度学习模型在外部验证数据集中同样显示出良好的性能,模型C和模型D的AUC分别为0.887(95%CI:0.798~0.960)和0.947(95%CI:0.891~0.984)。结论基于MRI-DWI的影像组学特征在预测接受静脉溶栓治疗的AIS患者的90天预后中发挥重要作用。深度学习方法在AIS溶栓治疗预后的预测模型中优于传统机器学习方法。结合临床特征和MRI-DWI特征的深度学习模型可为临床个性化评估AIS患者预后及制订治疗方案提供有力工具。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
基金This work was supported by grants from the Ministry of Science and Technology and the Ministry of Health of the People’s Republic of China(National S&T Major Project of China:2011BAI08B02,2012ZX09303,2013BAI09B14,2013BAI09B03,2015BAI12B02,2015BAI12B04,2017YFC1310900,2017YFC1310901 and 2017YFC1310903)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2013BAI09B03)+1 种基金Beijing Municipal Committee of Science and Technology(D15110700200000,D151100002015001,D151100002015002,Z161100000516223 and Z141107002514125)Beijing Institute for Brain Disorders(BIBD-PXM2013_014226_07_000084).
文摘Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This article outlines its objectives,operational structure,patient population,quality improvement(QI)intervention tools,data elements,data collection methodology and current patient and hospital data.Methods The CSCA is a national,hospital-based,multicentre,voluntary,multifaceted intervention and continuous QI initiative.This multifaceted intervention includes stroke centre development,written care protocols,workshops and a monitoring/feedback system of evidencebased performance measures.The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital.results As of July 2017,1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433264 patients with acute stroke/transient ischaemic attacks(TIA),including 352572(81.38%)acute ischaemic stroke,30362(7.01%)TIA,42080(9.71%)spontaneous intracranial haemorrhage,5505(1.27%)subarachnoid haemorrhage and 2745(0.63%)not specified stroke.Conclusion The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and,ultimately,improve patient outcomes.It supports the CSA mission to reduce stroke burden in China.
基金supported by the National Natural Science Foundation of China(82071467)the International(Regional)Cooperation and Exchange Program of the National Natural Science Foundation of China(82111330075)+3 种基金the National Natural Science Foundation for Youth Scholars of China(81801053)the Innovation Team Support Plan of Universities in Liaoning Province(LT2019015)the Liaoning Provincial Key Research and Development Guidance Program(2019JH8/10300002)the Liaoning Revitalization Talents Plan(XLYC1802097).
文摘Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia.However,con-ventional bulk sequencing makes it challenging to depict this complex immune network.Using single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune cells.Microglia were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal regeneration.Trajectory inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated MDMs.Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying mechanisms.This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
文摘目的构建基于MRI扩散加权成像(diffusion-weighted imaging,DWI)的深度学习模型,讨论其对急性缺血性卒中静脉溶栓治疗患者90天预后的预测价值。材料与方法回顾性分析了2家医院进行静脉溶栓治疗的677名急性缺血性卒中(acute ischemic stroke,AIS)患者的临床及影像学资料,通过影像储存和传输系统(picture archiving and communication systems,PACS)收集患者MRI-DWI图像,使用深度神经网络提取患者图像特征。我们将数据集1(医院1)随机分为训练集(70%)和测试集(30%),建立基于临床特征(模型A)和MRI-DWI影像组学特征(模型B)的传统机器学习模型,基于MRI-DWI深度学习特征的深度学习模型(模型C)以及结合临床特征和深度学习特征的组合模型(模型D),预测AIS患者接受静脉溶栓治疗后90天预后[通过评估改良Rankin评分(modified Rankin Scale,mRS),评分<2分表示预后良好]。数据集2(医院2)用于外部验证。通过受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under the curve,AUC)评估模型的预测性能。为了比较不同模型的AUC值差异是否有统计学意义,进一步采用DeLong检验进行统计分析,评估各模型之间AUC差异的显著性。结果基于临床特征和DWI-MRI影像组学特征的机器学习模型A和模型B以及深度学习模型C的AUC分别为0.705[95%置信区间(confidence interval,CI):0.613~0.792]、0.846(95%CI:0.777~0.906)和0.877(95%CI:0.811~0.934)。结合临床和深度学习特征的组合模型D在预测AIS患者静脉溶栓后90天预后方面表现出显著优势,其AUC值为0.930(95%CI:0.890~0.963)。此外,深度学习模型在外部验证数据集中同样显示出良好的性能,模型C和模型D的AUC分别为0.887(95%CI:0.798~0.960)和0.947(95%CI:0.891~0.984)。结论基于MRI-DWI的影像组学特征在预测接受静脉溶栓治疗的AIS患者的90天预后中发挥重要作用。深度学习方法在AIS溶栓治疗预后的预测模型中优于传统机器学习方法。结合临床特征和MRI-DWI特征的深度学习模型可为临床个性化评估AIS患者预后及制订治疗方案提供有力工具。
