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.

Small Vessel Disease: Neuropathology

2003 ◽  
Vol 15 (S1) ◽  
pp. 67-69 ◽  
Author(s):  
David G. Munoz
Keyword(s):  
Blood Vessels ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Cerebral Blood Vessels ◽  
Vessel Disease ◽  
Different Populations

Diseases of small cerebral blood vessels are heterogeneous in etiology and manifestations. Lipohyalinosis, venous collagenosis, amyloid angiopathy, and CADASIL affect different populations of blood vessels. Large and small hemorrhages, lacunae, cortical microinfarcts, and leukoaraiosis are the most important consequences of the small vessel angiopathies. Altered permeability as well as ischemia may be involved in the pathogenesis of the latter.

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.

Abstract 3208: Sensitivity and Reliability of SWI Compared to T2* GRE MRI for Detection of Microbleeds in Cerebral Amyloid Angiopathy

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ah-Ling Cheng ◽  
Cheryl R McCreary ◽  
M. L Lauzon ◽  
Richard Frayne ◽  
Mayank Goyal ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Intraclass Correlation ◽  
Case Series ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Healthy Controls ◽  
Vessel Disease ◽  
Cerebral Amyloid

Introduction: Case examples and small case series suggest that MRI susceptibility weighted imaging (SWI) may be more sensitive for cerebral microbleed (CMB) detection compared to MRI T2* gradient-recalled echo (GRE). However, there are few data on CMB counts measured by SWI vs. GRE, or inter-rater reliability, in groups of patients with cerebral small vessel disease. We used data from a prospective cohort study of cerebral amyloid angiopathy (CAA), a cerebral small-vessel disease marked by high numbers of CMBs, to quantify the sensitivity and reliability of SWI vs. GRE for CMB detection. Methods: Nine patients with symptomatic CAA (mean age 71±8.3; 7 males and 2 females) and 21 healthy non-CAA controls (mean age 68±6.3; 10 M/11 F) underwent T2* GRE and SWI on a 3.0T MR scanner. Probable CAA was diagnosed according to the Boston criteria prior to study entry using information from clinical MRI with GRE sequences. Two raters (labeled 1 and 2) independently interpreted the GRE and SWI scans blinded to clinical information. The phase-filtered magnitude image was used for SWI interpretation. Agreement reliability was assessed using the kappa coefficient (where a kappa of ≥0.60 indicates good agreement) or the intraclass correlation coefficient (ICC). Results: Overall, the raters identified 1,432 CMBs in the 9 CAA cases (range 1-434 per patient) and 8 CMBs in the healthy controls (range 0-3). Rater 1 identified CMBs in 5/21 healthy controls on SWI and 5/21 on GRE, while rater 2 identified CMBs in 4/21 on SWI and 3/21 on GRE (kappa 0.70 for GRE and 0.57 for SWI). In CAA cases more CMBs were seen on SWI compared to the GRE sequence but the difference was significant only for rater 1 (rater 1: on average 85% more per patient on SWI than on GRE, p=0.008; rater 2: 19% more, p=0.25). Among CAA cases the reliability between raters was poor for GRE (ICC 0.36) but excellent for SWI (0.94, p<0.05 for comparison with GRE). Review suggested that the differing reliability was because rater 1 was less likely than rater 2 to identify faint lesions on GRE as CMB, whereas these lesions were more conspicuous on SWI. If SWI rather than GRE were used to determine CAA status according to the Boston criteria, all 9 CAA cases would remain classified as probable CAA but 2/21 controls would be reclassified as either possible (n=1) or probable (n=1) asymptomatic CAA based on the detection of one or more lobar microbleeds on SWI. Conclusions: SWI confers greater reliability as well as greater sensitivity for CMB detection compared to GRE, and should be the preferred sequence for quantifying CMBs. SWI may more frequently identify lobar microbleeds that could represent asymptomatic CAA. Further research is needed to determine whether the Boston criteria require revision to take into account the greater sensitivity of SWI for CMB detection.

Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011932
Author(s):  
Juan Pablo Castello ◽  
Marco Pasi ◽  
Jessica R Abramson ◽  
Axana Rodriguez-Torres ◽  
Sandro Marini ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Ethnic Differences ◽  
Small Vessel Disease ◽  
Ethnic Disparities ◽  
Recurrence Risk ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Racial Ethnic

Objective:Black and Hispanic survivors of Intracerebral Hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic Cerebral Small Vessel Disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk.Methods:We analyzed data from the Massachusetts General Hospital ICH study (MGH-ICH, n=593) and the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n= 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk.Results:We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p=0.011) and HTNA burden (p=0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05).Conclusions:We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial / ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity, and investigating social determinants of health.

scholarly journals Cerebral small vessel disease: classification, clinical manifestations, diagnosis, and features of treatment

2019 ◽  
Vol 11 (3S) ◽  
pp. 4-17 ◽  
Author(s):  
A. A. Kulesh ◽  
V. E. Drobakha ◽  
V. V. Shestakov
Keyword(s):  
Hemorrhagic Stroke ◽  
Small Vessel Disease ◽  
Clinical Manifestations ◽  
Cerebrovascular Diseases ◽  
Cerebral Small Vessel Disease ◽  
Point Of View ◽  
Disease Classification ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease

The paper considers the relevance of the problem of cerebral small vessel disease (CSVD) that is an important cause of ischemic and hemorrhagic stroke, associated with the development of cognitive impairment and complications of antithrombotic therapy. It presents briefly the current issues of etiology and pathogenesis of the disease. Sporadic non-amyloid microangiopathy, cerebral amyloid angiopathy, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are discussed in detail from the point of view of their clinical presentation, neuroimaging, and features of therapeutic tactics. An algorithm for diagnosing CSVD in patients admitted to hospital for stroke and a differentiated approach to their treatment are proposed. Consideration of the neuroimaging manifestations of CSVD is noted to be necessary for the safe and more effective treatment of patients with cerebrovascular diseases.

Prevention of Cerebral Small Vessel Disease

2017 ◽  
Vol 37 (03) ◽  
pp. 316-325 ◽  
Author(s):  
Eric Smith
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Unmet Need ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Cerebral Amyloid

AbstractCerebral small vessel disease can cause either ischemic stroke or intracerebral hemorrhage. Accounting for up to 25% of all strokes, it is also the second biggest contributor to the risk of dementia, and is the most common incidentally discovered finding on brain imaging. There are two main causes of cerebral small vessel disease: arteriolosclerotic small vessel disease (with hypertension as the main modifiable risk factor) and cerebral amyloid angiopathy (predominantly caused by β-amyloid deposits limited to the cerebral small arteries, arterioles, and capillaries). Prevention should include the treatment of hypertension and diabetes, if present, and the modification of lifestyle factors such as obesity and poor nutrition. Patients with small subcortical ischemic strokes should be treated with antithrombotics; dual antiplatelet therapy may be more effective than aspirin for the first 3 weeks following acute stroke, but is not more effective than aspirin for long-term prevention. Unresolved questions include the effectiveness of nonaspirin prevention strategies to prevent early recurrence or stroke extension in small subcortical ischemic stroke, and whether symptomatic or silent small vessel disease should influence decisions regarding selection for carotid revascularization or anticoagulation for atrial fibrillation. There is an unmet need for disease-modifying preventive therapies for cerebral amyloid angiopathy, the second most-common cause of spontaneous intracerebral hemorrhage.

Neuropathology of Vascular Brain Health: Insights From Ex Vivo Magnetic Resonance Imaging–Histopathology Studies in Cerebral Small Vessel Disease

Stroke ◽  
2022 ◽  
Author(s):  
Susanne J. van Veluw ◽  
Konstantinos Arfanakis ◽  
Julie A. Schneider
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Human Brain ◽  
Small Vessel Disease ◽  
Ex Vivo ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Resonance Imaging ◽  
Vessel Disease

Sporadic cerebral small vessel disease (SVD) is a major contributor to vascular cognitive impairment and dementia in the aging human brain. On neuropathology, sporadic SVD is characterized by abnormalities to the small vessels of the brain predominantly in the form of cerebral amyloid angiopathy and arteriolosclerosis. These pathologies frequently coexist with Alzheimer disease changes, such as plaques and tangles, in a single brain. Conversely, during life, magnetic resonance imaging (MRI) only captures the larger manifestations of SVD in the form of parenchymal brain abnormalities. There appears to be a major knowledge gap regarding the underlying neuropathology of individual MRI-detectable SVD abnormalities. Ex vivo MRI in postmortem human brain tissue is a powerful tool to bridge this gap. This review summarizes current insights into the histopathologic correlations of MRI manifestations of SVD, their underlying cause, presumed pathophysiology, and associated secondary tissue injury. Moreover, we discuss the advantages and limitations of ex vivo MRI-guided histopathologic investigations and make recommendations for future studies.

scholarly journals Cerebral Small Vessel Disease and Cerebral Amyloid Angiopathy

2019 ◽  
Author(s):  
Raffaella Valenti
Keyword(s):  
Cognitive Rehabilitation ◽  
Small Vessel Disease ◽  
Prognostic Significance ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Elderly Subjects ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Cerebral Amyloid ◽  
The Brain

Sporadic cerebral small vessel disease (SVD) is considered to be among the most commonly known neuropathological processes in the brain, hosting a crucial role in stroke, cognitive impairment, and functional loss in elderly subjects. We investigated clinical (neuroimaging and cognitive) biomarkers in the SVD, through a series of analyses from our five studies. Sporadic cerebral SVD is a complex ‘micro-world’ to be globally considered. All the relevant lesion types and SVD neuroimaging burden should be taken into account. The cumulative effects of microangiopathy burden in the brain of patients affected by SVD are crucial. Cognitive rehabilitation could represent a promising approach to prevent vascular dementia or to improve cognitive performances in patients with cerebral SVD. Longitudinal studies may provide more robust information about the progression and prognostic significance of our findings.

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 Significance of Cortical Micro-Infarcts in the Human Brain

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Jacques L De Reuck
Keyword(s):  
Vascular Dementia ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
White Matter Changes ◽  
Vessel Disease ◽  
Neurodegenerative Dementia ◽  
Cerebral Amyloid

Cortical micro-infarcts are due to cerebral small vessel disease. In contrast to the arteriosclerotic type of cerebral small vessel disease, cortical micro-infarcts are mainly related and due to cerebral amyloid angiopathy. Alzheimer’s disease is the most frequent neurodegenerative dementia disease associated to cerebral amyloid angiopathy and cortical micro-infarcts. Vascular dementia cannot only be due to lacunar infarcts and ischemic white matter changes, but can also be caused by cortical micro-infarcts. The latter are a frequent cause of vascular dementia and decrease globally the cerebral blood flow.

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