Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
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
Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Dep...Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group(28 patients)and a control group(33 patients)by lottery method.The control group received conventional nursing care,while the observation group received progressive muscle relaxation training interventions in addition to the conventional care.The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Scale(HAMD),and the Stroke-Specific Quality of Life Scale(SS-QOL)were used to compare the effects before the intervention,7 days after the intervention,and 30 days after the intervention.Results:Over time,at different time points after the intervention,the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group(P<0.05).The quality of life scores were significantly higher in the observation group compared to the control group(P<0.05),and these differences were statistically significant.Conclusion:Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.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
Differences in the imaging subgroups of cerebral small vessel disease(CSVD)need to be further explored.First,we use propensity score matching to obtain balanced datasets.Then random forest(RF)is adopted to classify th...Differences in the imaging subgroups of cerebral small vessel disease(CSVD)need to be further explored.First,we use propensity score matching to obtain balanced datasets.Then random forest(RF)is adopted to classify the subgroups compared with support vector machine(SVM)and extreme gradient boosting(XGBoost),and to select the features.The top 10 important features are included in the stepwise logistic regression,and the odds ratio(OR)and 95%confidence interval(CI)are obtained.There are 41290 adult inpatient records diagnosed with CSVD.Accuracy and area under curve(AUC)of RF are close to 0.7,which performs best in classification compared to SVM and XGBoost.OR and 95%CI of hematocrit for white matter lesions(WMLs),lacunes,microbleeds,atrophy,and enlarged perivascular space(EPVS)are 0.9875(0.9857−0.9893),0.9728(0.9705−0.9752),0.9782(0.9740−0.9824),1.0093(1.0081−1.0106),and 0.9716(0.9597−0.9832).OR and 95%CI of red cell distribution width for WMLs,lacunes,atrophy,and EPVS are 0.9600(0.9538−0.9662),0.9630(0.9559−0.9702),1.0751(1.0686−1.0817),and 0.9304(0.8864−0.9755).OR and 95%CI of platelet distribution width for WMLs,lacunes,and microbleeds are 1.1796(1.1636−1.1958),1.1663(1.1476−1.1853),and 1.0416(1.0152−1.0687).This study proposes a new analytical framework to select important clinical markers for CSVD with machine learning based on a common data model,which has low cost,fast speed,large sample size,and continuous data sources.展开更多
BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD rema...BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD remains elusive.AIM To explore the association between intercellular adhesion molecule-1(ICAM-1)and blood-brain barrier(BBB)penetration in CSVD.METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community(Anhui,China)between December 2021 and March 2022.The study population comprised 142 patients,including 80 in the CSVD group and 62 in the control group.Depression was present in 53 out of 80 patients with CSVD.Multisequence magnetic resonance imaging(MRI)and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume,cortical thickness,and cortical area of each brain region.Moreover,neuropsychological tests including the Hamilton depression scale,mini-mental state examination,and Montreal cognitive assessment basic scores were performed.RESULTS The multivariable analysis showed that age[P=0.011;odds ratio(OR)=0.930,95%confidence interval(CI):0.880-0.983]and ICAM-1 levels(P=0.023;OR=1.007,95%CI:1.001-1.013)were associated with CSVD.Two regions of interest(ROIs;ROI3 and ROI4)in the white matter showed significant(both P<0.001;95%CI:0.419-0.837 and 0.366-0.878)differences between the two groups,whereas only ROI1 in the gray matter showed signi-ficant difference(P=0.046;95%CI:0.007-0.680)between the two groups.ICAM-1 was significantly correlated(all P<0.05)with cortical thickness in multiple brain regions in the CSVD group.CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD.ICAM-1 may be associated with cortical thickness in the brain,predominantly in the white matter,and a significant increase in BBB permeability,proposing the involvement of ICAM-1 in BBB destruction.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
Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often a...Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often asymptomatic in its early stages.However,as CsvD develops,brain disorders may occur,such as stroke,cognitive dysfunction,dyskinesia and mood disorders,and heart,kidney,eye and systemic disorders.As the population continues to age,the burden of CsvD is increasing.Moreover,there is an urgent need for better screening methods and diagnostic markers for CsvD,in addition to preventive and asymptomatic-and mild-stage treatments.Integrative medicine(IM),which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives,has unique advantages for the prevention and treatment of CsvD.In this review,we summarize the biological markers,ultrasound and imaging features,disease-related genes and risk factors relevant to CsvD diagnosis and screening.Furthermore,we discuss IM-based csvD prevention and treatment strategies to stimulate further research in this field.展开更多
Objective: Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD)...Objective: Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources: We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of"hypertension", "cerebral small vessel disease", "'white matter lesions", "enlarged perivascular spaces", "lacunar infarcts", "cerebral microbleeds", and "cognitive impairment" in the database of PubMed. Study Selection: Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results: In recent years, studies have demonstrated that hypertension-related changes (e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy) can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure (BP) control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions: We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.展开更多
We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospectiv...We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.展开更多
The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivas...The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.The CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.展开更多
Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population.The widespread application of and ...Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population.The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD.In this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.展开更多
Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological ba...Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.展开更多
Objective: Photobiomodulation (also known as Low Level Laser. LLLT or Cold Laser;Photo Medicine (PM)) has been a vital adjunct therapy in our clinical practice over 5 years, observations of improvement in cognition an...Objective: Photobiomodulation (also known as Low Level Laser. LLLT or Cold Laser;Photo Medicine (PM)) has been a vital adjunct therapy in our clinical practice over 5 years, observations of improvement in cognition and personality were noted in several patients. As a result, selected patients with Alzheimer’s Disease, vascular dementia, post-traumatic brain injury and other neuro-degenerative diseases were treated at clinical practices in Buffalo, New York;Sarasota, Florida;Lafayette, Indiana;Phoenix, Az., and Baton Rouge, La. Over 60 patients were treated with an average of 4 times over an 8-day period all reported/exhibited improvement in their condition, except that two men who were in their seventies were in robust health but had no short-term memory and no improvement was observed. However, Theralase has developed a more efficacious system which will be more efficacious, due to increased power for ATP activation. Method: Over 150 patients with the above conditions were treated in various areas (depending on diagnosis) including the prefrontal cortex, temporal lobe, Hippocampus, and Circle of Willis for duration of two and one-half minutes every 48 hours for 5 - 6 treatments. We utilized the Theralase multi-probe (905 nm/660 nm) at 60 miliwatts. It utilizes 5 - 905 nm near infra-red diodes and 4 infra-red 660 laser diodes with a peak power of 50,000 milliwatts at peak and pulse duration of 200 nanoseconds [1]. The PTSD patients were evaluated utilizing the co-occurring disorders program screening and assessment form. Conclusion: Dementia patients exhibited varying degrees of improvement in cognitive function and personality, leading to improved quality of life and decreased caregiver burden. PTSD patients’ improvement was objectively measured by formal neuropsychological testing utilizing the form. All PTSD patients scored no emotional problems after 3 - 5 treatments and all experienced overall sense of well-being. One experienced return of ability to smell he had not had for 5 years. Similar results were reported in a Japanese study where 15 patients were followed for a year. This non-invasive and non-systemic modality of therapy could play a key role in treating progressive neurodegenerative conditions, improving quality of life, and reducing health care costs.展开更多
Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leuko...Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL).Recently,increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease(CSVD)with an autosomal dominant pattern of inheritance.This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.Methods:We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1,2020.CARASIL probands with genetic diagnosis reported to date were also reviewed.The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.Results:Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included.Compared with typical CARASIL,HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors(P<0.001),a later onset age(P<0.001),and a relatively slower clinical progression.Alopecia and spondylosis can be observed,but less than those in the typical CARASIL.Thirty-five heterozygous mutations in HTRA1 were reported,most of which were missense mutations.Amino acids located close to amino acids 250-300 were most frequently affected,followed by these located near 150∼200.While amino acids 250∼300 were also the most frequently affected region in CARASIL patients,fewer mutations precede the 200th amino acids were detected,especially in the Kazal-type serine protease domain.Conclusions:HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL.The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.展开更多
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hype...Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.展开更多
Objective To investigate the relationship betweentotal cerebral small vessel disease (CSVD) burden andintracranial hemorrhage transformation (HT) after intravenousthrombolysis in patients with acute ischemicstroke (AI...Objective To investigate the relationship betweentotal cerebral small vessel disease (CSVD) burden andintracranial hemorrhage transformation (HT) after intravenousthrombolysis in patients with acute ischemicstroke (AIS). Methods One hundred and fifty-four patientswho suffered from ischemic stroke within 4. 5 hoursof onset and received recombinant tissue plasminogen activatorthrombolytic therapy in the emergency green channelof the First Affiliated Hospital of Soochow Universityfrom August 2016 to January 2018 were enrolled. HT examinedby computed tomography scan within 24 hours afterthrombolysis was included. The magnetic resonanceimaging examination was performed within 48 hours. Thepatients were divided into two groups: HT group andcontrol group according to the presence or absence ofHT.展开更多
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
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Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group(28 patients)and a control group(33 patients)by lottery method.The control group received conventional nursing care,while the observation group received progressive muscle relaxation training interventions in addition to the conventional care.The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Scale(HAMD),and the Stroke-Specific Quality of Life Scale(SS-QOL)were used to compare the effects before the intervention,7 days after the intervention,and 30 days after the intervention.Results:Over time,at different time points after the intervention,the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group(P<0.05).The quality of life scores were significantly higher in the observation group compared to the control group(P<0.05),and these differences were statistically significant.Conclusion:Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.
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 the National Natural Science Foundation of China(Nos.72204169 and 81825007)Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910025030)+5 种基金Capital’s Funds for Health Improvement and Research(No.2022-2-2045)National Key R&D Program of China(Nos.2022YFF15015002022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,and 2022YFF1501505)Youth Beijing Scholar Program(No.010)Beijing Laboratory of Oral Health(No.PXM2021_014226_000041)Beijing Talent Project-Class A:Innovation and Development(No.2018A12)National Ten-Thousand Talent PlanLeadership of Scientific and Technological Innovation,and National Key R&D Program of China(Nos.2017YFC1307900 and 2017YFC1307905).
文摘Differences in the imaging subgroups of cerebral small vessel disease(CSVD)need to be further explored.First,we use propensity score matching to obtain balanced datasets.Then random forest(RF)is adopted to classify the subgroups compared with support vector machine(SVM)and extreme gradient boosting(XGBoost),and to select the features.The top 10 important features are included in the stepwise logistic regression,and the odds ratio(OR)and 95%confidence interval(CI)are obtained.There are 41290 adult inpatient records diagnosed with CSVD.Accuracy and area under curve(AUC)of RF are close to 0.7,which performs best in classification compared to SVM and XGBoost.OR and 95%CI of hematocrit for white matter lesions(WMLs),lacunes,microbleeds,atrophy,and enlarged perivascular space(EPVS)are 0.9875(0.9857−0.9893),0.9728(0.9705−0.9752),0.9782(0.9740−0.9824),1.0093(1.0081−1.0106),and 0.9716(0.9597−0.9832).OR and 95%CI of red cell distribution width for WMLs,lacunes,atrophy,and EPVS are 0.9600(0.9538−0.9662),0.9630(0.9559−0.9702),1.0751(1.0686−1.0817),and 0.9304(0.8864−0.9755).OR and 95%CI of platelet distribution width for WMLs,lacunes,and microbleeds are 1.1796(1.1636−1.1958),1.1663(1.1476−1.1853),and 1.0416(1.0152−1.0687).This study proposes a new analytical framework to select important clinical markers for CSVD with machine learning based on a common data model,which has low cost,fast speed,large sample size,and continuous data sources.
基金Supported by National Natural Science Foundation of China,No.81573807。
文摘BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD remains elusive.AIM To explore the association between intercellular adhesion molecule-1(ICAM-1)and blood-brain barrier(BBB)penetration in CSVD.METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community(Anhui,China)between December 2021 and March 2022.The study population comprised 142 patients,including 80 in the CSVD group and 62 in the control group.Depression was present in 53 out of 80 patients with CSVD.Multisequence magnetic resonance imaging(MRI)and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume,cortical thickness,and cortical area of each brain region.Moreover,neuropsychological tests including the Hamilton depression scale,mini-mental state examination,and Montreal cognitive assessment basic scores were performed.RESULTS The multivariable analysis showed that age[P=0.011;odds ratio(OR)=0.930,95%confidence interval(CI):0.880-0.983]and ICAM-1 levels(P=0.023;OR=1.007,95%CI:1.001-1.013)were associated with CSVD.Two regions of interest(ROIs;ROI3 and ROI4)in the white matter showed significant(both P<0.001;95%CI:0.419-0.837 and 0.366-0.878)differences between the two groups,whereas only ROI1 in the gray matter showed signi-ficant difference(P=0.046;95%CI:0.007-0.680)between the two groups.ICAM-1 was significantly correlated(all P<0.05)with cortical thickness in multiple brain regions in the CSVD group.CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD.ICAM-1 may be associated with cortical thickness in the brain,predominantly in the white matter,and a significant increase in BBB permeability,proposing the involvement of ICAM-1 in BBB destruction.
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.
基金Supported by the National Natural Science Foundation of China(No.82074507 and No.81904263)Chinese Medicine Research Project Plan of Fujian Province in 2021-2024(No.2021ZYJC02)Clinical Special Project of Fujian University of Traditional Chinese Medicine(No.XB2021038)。
文摘Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often asymptomatic in its early stages.However,as CsvD develops,brain disorders may occur,such as stroke,cognitive dysfunction,dyskinesia and mood disorders,and heart,kidney,eye and systemic disorders.As the population continues to age,the burden of CsvD is increasing.Moreover,there is an urgent need for better screening methods and diagnostic markers for CsvD,in addition to preventive and asymptomatic-and mild-stage treatments.Integrative medicine(IM),which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives,has unique advantages for the prevention and treatment of CsvD.In this review,we summarize the biological markers,ultrasound and imaging features,disease-related genes and risk factors relevant to CsvD diagnosis and screening.Furthermore,we discuss IM-based csvD prevention and treatment strategies to stimulate further research in this field.
文摘Objective: Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources: We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of"hypertension", "cerebral small vessel disease", "'white matter lesions", "enlarged perivascular spaces", "lacunar infarcts", "cerebral microbleeds", and "cognitive impairment" in the database of PubMed. Study Selection: Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results: In recent years, studies have demonstrated that hypertension-related changes (e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy) can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure (BP) control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions: We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.
基金supported by the National Key Research and Development Program of China(2016YFB1001402)National Natural Science Foundation of China(81971138)+2 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-3-008)Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)Research Foundation for Young Scholars of Peking Union Medical College Hospital(PUMCH201911275)。
文摘We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.
基金supported partially by grants from the National Key Research and Development Program of China(No.2016YFC1300600)Research Grants Council of the Hong Kong Special Administrative Region,China(No.CUHK 14204117)。
文摘The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.The CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.
基金the National Key Research and Development Program of China(No.2016YFC13600600).
文摘Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population.The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD.In this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.
文摘Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.
文摘Objective: Photobiomodulation (also known as Low Level Laser. LLLT or Cold Laser;Photo Medicine (PM)) has been a vital adjunct therapy in our clinical practice over 5 years, observations of improvement in cognition and personality were noted in several patients. As a result, selected patients with Alzheimer’s Disease, vascular dementia, post-traumatic brain injury and other neuro-degenerative diseases were treated at clinical practices in Buffalo, New York;Sarasota, Florida;Lafayette, Indiana;Phoenix, Az., and Baton Rouge, La. Over 60 patients were treated with an average of 4 times over an 8-day period all reported/exhibited improvement in their condition, except that two men who were in their seventies were in robust health but had no short-term memory and no improvement was observed. However, Theralase has developed a more efficacious system which will be more efficacious, due to increased power for ATP activation. Method: Over 150 patients with the above conditions were treated in various areas (depending on diagnosis) including the prefrontal cortex, temporal lobe, Hippocampus, and Circle of Willis for duration of two and one-half minutes every 48 hours for 5 - 6 treatments. We utilized the Theralase multi-probe (905 nm/660 nm) at 60 miliwatts. It utilizes 5 - 905 nm near infra-red diodes and 4 infra-red 660 laser diodes with a peak power of 50,000 milliwatts at peak and pulse duration of 200 nanoseconds [1]. The PTSD patients were evaluated utilizing the co-occurring disorders program screening and assessment form. Conclusion: Dementia patients exhibited varying degrees of improvement in cognitive function and personality, leading to improved quality of life and decreased caregiver burden. PTSD patients’ improvement was objectively measured by formal neuropsychological testing utilizing the form. All PTSD patients scored no emotional problems after 3 - 5 treatments and all experienced overall sense of well-being. One experienced return of ability to smell he had not had for 5 years. Similar results were reported in a Japanese study where 15 patients were followed for a year. This non-invasive and non-systemic modality of therapy could play a key role in treating progressive neurodegenerative conditions, improving quality of life, and reducing health care costs.
基金supported by grants from the National Key Research and Development Program of China(No.2016YFC0901004)the CAMS Innovation Fund for Medical Sciences(CIFMS#2017-I2M-3-008)。
文摘Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL).Recently,increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease(CSVD)with an autosomal dominant pattern of inheritance.This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.Methods:We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1,2020.CARASIL probands with genetic diagnosis reported to date were also reviewed.The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.Results:Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included.Compared with typical CARASIL,HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors(P<0.001),a later onset age(P<0.001),and a relatively slower clinical progression.Alopecia and spondylosis can be observed,but less than those in the typical CARASIL.Thirty-five heterozygous mutations in HTRA1 were reported,most of which were missense mutations.Amino acids located close to amino acids 250-300 were most frequently affected,followed by these located near 150∼200.While amino acids 250∼300 were also the most frequently affected region in CARASIL patients,fewer mutations precede the 200th amino acids were detected,especially in the Kazal-type serine protease domain.Conclusions:HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL.The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.
基金This work was supported by National Natural Science Foundation of China(Grants No.81873727 and 82171196).
文摘Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.
文摘Objective To investigate the relationship betweentotal cerebral small vessel disease (CSVD) burden andintracranial hemorrhage transformation (HT) after intravenousthrombolysis in patients with acute ischemicstroke (AIS). Methods One hundred and fifty-four patientswho suffered from ischemic stroke within 4. 5 hoursof onset and received recombinant tissue plasminogen activatorthrombolytic therapy in the emergency green channelof the First Affiliated Hospital of Soochow Universityfrom August 2016 to January 2018 were enrolled. HT examinedby computed tomography scan within 24 hours afterthrombolysis was included. The magnetic resonanceimaging examination was performed within 48 hours. Thepatients were divided into two groups: HT group andcontrol group according to the presence or absence ofHT.