Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate th...BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.展开更多
Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the patholo...Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.展开更多
目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、...目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,根据磁共振DWI分为近期皮质下小梗死(RSSI)组和非RSSI组,统计RSSI的部位和数目。比较两组患者的一般人口学资料、临床资料、认知功能,分析RSSI影像学特征与认知功能的关系。结果 共纳入CSVD患者181例,RSSI组91例,非RSSI组90例。RSSI组与非RSSI组相比,BMI高[(25.43±3.53)kg/m^(2) vs(24.27±3.33)kg/m^(2),t=2.228, P=0.027],收缩压高[(145.3±16.2)mmHg vs(139.6±20.2)mmHg,t=2.013,P=0.046],MoCA总分较低[22(18.8,26) vs 24(21,27),Z=-1.980,P=0.048],视空间与执行能力[3(2,4) vs 4(3,5),Z=-2.756,P=0.006]、语言[2(2,3) vs 2(1,2), Z=-2.020,P=0.043]、抽象[2(1,2) vs 2(1,2)分,Z=-2.052,P=0.04]得分均较低,差异均具有显著性统计学意义(P<0.05)。RSSI基底节梗死组与非RSSI组相比,MoCA总分较低[21(17,23) vs 24(21,27),Z=-2.018,P=0.044],视空间与执行[3(1.5,3.5) vs 4(3,5),Z=-2.601,P=0.009]得分较低,RSSI脑干梗死组与非RSSI组相比,视空间与执行[3(2,4) vs 4(3,5),Z=-2.325,P=0.020]、语言[2(1,2) vs 2(2,3),Z=-2.338,P=0.019]得分较低,差异具有显著性统计学意义。结论 CSVD患者中RSSI可导致认知功能障碍,与RSSI梗死部位相关,RSSI不同梗死部位导致不同的认知损害模式。预防RSSI发生,对于预防CSVD相关认知功能障碍具有重要意义。展开更多
目的探讨水蛭治疗脑小血管病(Cerebral Small Vessel Disease,CSVD)所致神经功能障碍患者的临床疗效。方法选取2020年10月—2023年6月广西壮族自治区民族医院神经内科收治的120例CSVD导致认知功能障碍患者为研究对象,以随机数表法分为...目的探讨水蛭治疗脑小血管病(Cerebral Small Vessel Disease,CSVD)所致神经功能障碍患者的临床疗效。方法选取2020年10月—2023年6月广西壮族自治区民族医院神经内科收治的120例CSVD导致认知功能障碍患者为研究对象,以随机数表法分为对照组(n=60,常规西药内科基础治疗)和观察组(n=60,在对照组基础上增加中药水蛭治疗)。分别于治疗前、治疗2周及治疗3个月后观察两组患者的神经功能障碍评分和血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平。结果与治疗前相比,两组治疗2周、治疗3个月后的神经功能障碍评分以及血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平均明显下降,且观察组治疗3个月后下降幅度更大,差异有统计学意义(P均<0.05)。观察组治疗的总有效率(86.67%)高于对照组(71.67%),差异有统计学意义(χ^(2)=4.093,P<0.05)。结论水蛭能有效改善CSVD所致的神经功能缺损,同时能降低患者血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平。展开更多
脑小血管病(cerebral small vessel disease,CSVD)是一组临床、影像、病理综合征,主要累及颅内小血管,起病隐匿。CSVD与卒中、认知下降、情感障碍、步态异常及尿便失禁密切相关,给家庭和社会带来沉重的疾病负担和经济负担。但CSVD的致...脑小血管病(cerebral small vessel disease,CSVD)是一组临床、影像、病理综合征,主要累及颅内小血管,起病隐匿。CSVD与卒中、认知下降、情感障碍、步态异常及尿便失禁密切相关,给家庭和社会带来沉重的疾病负担和经济负担。但CSVD的致病机制仍不明确,临床诊断标准不统一,临床诊疗和试验研究面临重大挑战。本文旨在汇总当前CSVD的可能病因、发病机制和临床诊疗研究的进展及局限性,展望CSVD未来可能的临床研究方向。展开更多
脑小血管病(cerebral small vessel disease,CSVD)是引起人群认知功能障碍最重要的原因之一,随着我国人口老龄化趋势的加重及医学影像技术的发展,CSVD的发病率呈逐年上升趋势,其所引起的认知功能障碍也越来越受到关注。因脑小血管病起...脑小血管病(cerebral small vessel disease,CSVD)是引起人群认知功能障碍最重要的原因之一,随着我国人口老龄化趋势的加重及医学影像技术的发展,CSVD的发病率呈逐年上升趋势,其所引起的认知功能障碍也越来越受到关注。因脑小血管病起病隐匿、进展缓慢、早期无明显临床表现,出现症状时已进入认知功能障碍的中晚期或者已经形成痴呆,往往带给患者不能逆转的损伤及沉重的医疗负担。本文就不同影像学类型脑小血管病及其MRI总负荷对认知功能的影响进行综述,进一步了解CSVD与认知功能的关系,为CSVD所致认知功能障碍的识别和预防提供帮助。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82274611 (to LZ),82104419 (to DM)Capital Science and Technology Leading Talent Training Project,No.Z1 91100006119017 (to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803 (to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006 (to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017 (to DM)Beijing Gold-Bridge Project,No.ZZ20145 (to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
文摘BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.
基金supported by grants from the National Natural Science Foundation of China(32100798)the China Postdoctoral Science Foundation(2021M700821).
文摘Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.
文摘目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,根据磁共振DWI分为近期皮质下小梗死(RSSI)组和非RSSI组,统计RSSI的部位和数目。比较两组患者的一般人口学资料、临床资料、认知功能,分析RSSI影像学特征与认知功能的关系。结果 共纳入CSVD患者181例,RSSI组91例,非RSSI组90例。RSSI组与非RSSI组相比,BMI高[(25.43±3.53)kg/m^(2) vs(24.27±3.33)kg/m^(2),t=2.228, P=0.027],收缩压高[(145.3±16.2)mmHg vs(139.6±20.2)mmHg,t=2.013,P=0.046],MoCA总分较低[22(18.8,26) vs 24(21,27),Z=-1.980,P=0.048],视空间与执行能力[3(2,4) vs 4(3,5),Z=-2.756,P=0.006]、语言[2(2,3) vs 2(1,2), Z=-2.020,P=0.043]、抽象[2(1,2) vs 2(1,2)分,Z=-2.052,P=0.04]得分均较低,差异均具有显著性统计学意义(P<0.05)。RSSI基底节梗死组与非RSSI组相比,MoCA总分较低[21(17,23) vs 24(21,27),Z=-2.018,P=0.044],视空间与执行[3(1.5,3.5) vs 4(3,5),Z=-2.601,P=0.009]得分较低,RSSI脑干梗死组与非RSSI组相比,视空间与执行[3(2,4) vs 4(3,5),Z=-2.325,P=0.020]、语言[2(1,2) vs 2(2,3),Z=-2.338,P=0.019]得分较低,差异具有显著性统计学意义。结论 CSVD患者中RSSI可导致认知功能障碍,与RSSI梗死部位相关,RSSI不同梗死部位导致不同的认知损害模式。预防RSSI发生,对于预防CSVD相关认知功能障碍具有重要意义。
文摘目的探讨水蛭治疗脑小血管病(Cerebral Small Vessel Disease,CSVD)所致神经功能障碍患者的临床疗效。方法选取2020年10月—2023年6月广西壮族自治区民族医院神经内科收治的120例CSVD导致认知功能障碍患者为研究对象,以随机数表法分为对照组(n=60,常规西药内科基础治疗)和观察组(n=60,在对照组基础上增加中药水蛭治疗)。分别于治疗前、治疗2周及治疗3个月后观察两组患者的神经功能障碍评分和血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平。结果与治疗前相比,两组治疗2周、治疗3个月后的神经功能障碍评分以及血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平均明显下降,且观察组治疗3个月后下降幅度更大,差异有统计学意义(P均<0.05)。观察组治疗的总有效率(86.67%)高于对照组(71.67%),差异有统计学意义(χ^(2)=4.093,P<0.05)。结论水蛭能有效改善CSVD所致的神经功能缺损,同时能降低患者血清胱抑素C、同型半胱氨酸、高敏C反应蛋白指标水平。
文摘脑小血管病(cerebral small vessel disease,CSVD)是一组临床、影像、病理综合征,主要累及颅内小血管,起病隐匿。CSVD与卒中、认知下降、情感障碍、步态异常及尿便失禁密切相关,给家庭和社会带来沉重的疾病负担和经济负担。但CSVD的致病机制仍不明确,临床诊断标准不统一,临床诊疗和试验研究面临重大挑战。本文旨在汇总当前CSVD的可能病因、发病机制和临床诊疗研究的进展及局限性,展望CSVD未来可能的临床研究方向。
文摘脑小血管病(cerebral small vessel disease,CSVD)是引起人群认知功能障碍最重要的原因之一,随着我国人口老龄化趋势的加重及医学影像技术的发展,CSVD的发病率呈逐年上升趋势,其所引起的认知功能障碍也越来越受到关注。因脑小血管病起病隐匿、进展缓慢、早期无明显临床表现,出现症状时已进入认知功能障碍的中晚期或者已经形成痴呆,往往带给患者不能逆转的损伤及沉重的医疗负担。本文就不同影像学类型脑小血管病及其MRI总负荷对认知功能的影响进行综述,进一步了解CSVD与认知功能的关系,为CSVD所致认知功能障碍的识别和预防提供帮助。
