Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease

2017 ◽  
Vol 131 (10) ◽  
pp. 1001-1013 ◽  
Author(s):  
Friederike Held ◽  
Alan W.J. Morris ◽  
Daniel Pirici ◽  
Solveig Niklass ◽  
Matthew M.G. Sharp ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Small Vessel Disease ◽  
Collagen Iv ◽  
Cerebral Small Vessel Disease ◽  
Basement Membranes ◽  
Small Vessel ◽  
Small Vessels ◽  
Vessel Disease ◽  
Percentage Area ◽  
Β Amyloid

Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated through the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analyzed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks: (i) the percentage area immunostained for vascular collagen IV and laminin was quantified; (ii) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM); and (iii) the presence of vascular Aβ was assessed. Compared with controls, SHRSP exhibited a significantly higher percentage area immunostained with collagen IV in the striatum and thalamus. SHRSP also revealed an age-dependent increase of the capillary BM thickness and of endothelial vacuoles (caveolae) within subcortical regions. Endogenous Aβ deposits in the walls of small blood vessels were observed in the cortex (with the highest incidence found within fronto-parietal areas), striatum, thalamus and hippocampus. Vascular β-amyloid accumulations were frequently detected at sites of small vessel wall damage. Our data demonstrate changes in the expression of collagen IV and of the ultrastructure of BMs in the small vessels of SHRSP. Alterations are accompanied by vascular deposits of endogenous Aβ. Impaired β-amyloid clearance along perivascular and endothelial pathways and failure of extracellular Aβ degradation may be the key mechanisms connecting non-amyloid CSVD and CAA.

scholarly journals Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms

2020 ◽  
Vol 22 (2) ◽  
pp. 173-184
Author(s):  
Dao Pei Zhang ◽  
Suo Yin ◽  
Huai Liang Zhang ◽  
Dan Li ◽  
Bo Song ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Late Onset ◽  
Basic Research ◽  
Cerebral Small Vessel Disease ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Small Vessel ◽  
Predisposing Factor ◽  
Brain Vessels ◽  
Small Vessels ◽  
Vessel Disease

Intracranial arterial dolichoectasia (IADE), also known as dilatative arteriopathy of the brain vessels, refers to an increase in the length and diameter of at least one intracranial artery, and accounts for approximately 12% of all patients with stroke. However, the association of IADE with stroke is usually unclear. Cerebral small vessel disease (CSVD) is characterized by pathological changes in the small vessels. Clinically, patients with CSVD can be asymptomatic or present with stroke or cognitive decline. In the past 20 years, a series of studies have strongly promoted an understanding of the association between IADE and CSVD from clinical and pathological perspectives. It has been proposed that IADE and CSVD may be attributed to abnormal vascular remodeling driven by an abnormal matrix metalloproteinase/tissue inhibitor of metalloproteinase pathway. Also, IADErelated hemodynamic changes may result in initiation or progression of CSVD. Additionally, genetic factors are implicated in the pathogenesis of IADE and CSVD. Patients with Fabry’s disease and late-onset Pompe’s disease are prone to developing concomitant IADE and CSVD, and patients with collagen IV alpha 1 or 2 gene (<i>COL4A1/COL4A2</i>) and forkhead box C1 (<i>FOXC1</i>) variants present with IADE and CSVD. Race, strain, familial status, and vascular risk factors may be involved in the pathogenesis of IADE and CSVD. As well, experiments in mice have pointed to genetic strain as a predisposing factor for IADE and CSVD. However, there have been few direct genetic studies aimed towards determining the association between IADE and CSVD. In the future, more clinical and basic research studies are needed to elucidate the causal relationship between IADE and CSVD and the related molecular and genetic mechanisms.

scholarly journals Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

2020 ◽  
Vol 21 (11) ◽  
pp. 3862 ◽  
Author(s):  
Jayant Patwa ◽  
Swaran Jeet Singh Flora
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Blood Vessels ◽  
Small Vessel Disease ◽  
Vascular Dysfunction ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Antioxidant Defense Enzymes

Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

scholarly journals Cognitions and chronic cerebrovascular disease (small vessel disease)

2021 ◽  
Vol 17 (5) ◽  
pp. 76-81
Author(s):  
M.M. Oros
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Cerebrovascular Diseases ◽  
Cerebral Small Vessel Disease ◽  
Hereditary Diseases ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Small Vessels ◽  
Vessel Disease ◽  
Cognitive Deficiency

Vascular cognitive diseases (VCD) are the conditions when cerebrovascular diseases result in cognitive impairment. However, these diseases can lead by themselves to cognitive deficiency and amount to 15–30 % of dementia cases. It is important that age-associated cognitive impairments commonly resulted from comorbid vascular and neurogenerative pathologies. Among many mechanisms involving in VCD, cerebral small vessel disease is likely to be the most common and results in cognitive impairment regardless of the stroke. VCD is characterized by abnormalities affecting the brain structure and functioning of small vessels and manifests itself in numerous neuroimaging and neurologic signs. Cerebral small vessel disease is associated with various sporadic and hereditary diseases, which is the effect of the complex interrelation of genetic and vascular risk factors. The prevalence of cerebral small vessel disease increases with age, and the two most common sporadic types are arteriolosclerosis, which may be called hypertensive arteriopathy, and cerebral amyloid angiopathy. New approaches to the therapy enable to use the drugs directed at this pathology, which are available in Ukraine, particularly Ticolin and Dinar.

scholarly journals Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

2020 ◽  
Vol 5 (2) ◽  
pp. 128-137
Author(s):  
Huimin Chen ◽  
Yuesong Pan ◽  
Lixia Zong ◽  
Jing Jing ◽  
Xia Meng ◽  
...  
Keyword(s):  
Regression Models ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Arterial Stenosis ◽  
Small Vessel ◽  
Minor Stroke ◽  
Bleeding Events ◽  
Stroke Outcomes ◽  
Vessel Disease ◽  
Increased Risk

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589

scholarly journals Lenticulostriate artery combined with neuroimaging markers of cerebral small vessel disease differentiate the pathogenesis of recent subcortical infarction

2021 ◽  
pp. 0271678X2199262
Author(s):  
Shuai Jiang ◽  
Tian Cao ◽  
Yuying Yan ◽  
Tang Yang ◽  
Ye Yuan ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Branch Atheromatous Disease ◽  
Lenticulostriate Artery ◽  
Subcortical Infarction

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.

Total Cerebral Small Vessel Disease Score and Anthropometric Indices: A Population-Based Study in Older Adults of Amerindian Ancestry

2021 ◽  
pp. 1-4
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera
Keyword(s):  
Older Adults ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Population Based ◽  
Cerebral Small Vessel Disease ◽  
The Body ◽  
Small Vessel ◽  
Population Based Study ◽  
Vessel Disease ◽  
Ordinal Logistic Regression Model

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.

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