scholarly journals Perivascular spaces and brain waste clearance systems: relevance for neurodegenerative and cerebrovascular pathology

2021 ◽  
Author(s):  
Kaylene Gouveia-Freitas ◽  
António J. Bastos-Leite
Keyword(s):  
Basal Ganglia ◽  
Lymphatic Vessels ◽  
Vascular Wall ◽  
Lymphatic Drainage ◽  
Basement Membranes ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Functional Abnormality ◽  
Ischaemic Injury ◽  
Cerebrovascular Pathology

AbstractPerivascular spaces (PVS) of the brain, often called Virchow-Robin spaces, comprise fluid, cells and connective tissue, and are externally limited by astrocytic endfeet. PVS are involved in clearing brain waste and belong to the “glymphatic” system and/or the “intramural periarterial drainage” pathway through the basement membranes of the arteries. Related brain waste clearance systems include the blood–brain barrier, scavenger cells, cerebrospinal fluid, perineural lymphatic drainage pathways and the newly characterised meningeal lymphatic vessels. Any functional abnormality of PVS or related clearance systems might lead to accumulation of brain waste. It has been postulated that PVS enlargement can be secondary to accumulation of β-amyloid. Lack of integrity of the vascular wall, microbleeds, cerebral amyloid angiopathy (CAA) and enlarged PVS often occur in the preclinical stages of Alzheimer’s disease, preceding substantial brain atrophy. PVS enlargement in the form of état criblé at the basal ganglia has also been considered to reflect focal atrophy, most probably secondary to ischaemic injury, based upon both pathological and imaging arguments. In addition, distinct topographic patterns of enlarged PVS are related to different types of microangiopathy: CAA is linked to enlarged juxtacortical PVS, whereas subjects with vascular risk factors tend to have enlarged PVS in the basal ganglia. Therefore, enlarged PVS are progressively being regarded as a marker of neurodegenerative and cerebrovascular pathology. The present review addresses the evolving concept of PVS and brain waste clearance systems, the potential relevance of their dysfunction to neurodegenerative and cerebrovascular pathology, and potential therapeutic approaches of interest.

scholarly journals Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe

2020 ◽  
Vol 6 (50) ◽  
pp. eabc2697
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Chung Hwee Thiam ◽  
Syaza Hazwany Azhar ◽  
Caris Tan ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Lymphatic Transport ◽  
Atherosclerotic Plaques ◽  
Tissue Fluid ◽  
Atherosclerosis Progression ◽  
Lymphatic Vasculature ◽  
Lesion Regression ◽  
Transport Of Macromolecules

A functional lymphatic vasculature is essential for tissue fluid homeostasis, immunity, and lipid clearance. Although atherosclerosis has been linked to adventitial lymphangiogenesis, the functionality of aortic lymphatic vessels draining the diseased aorta has never been assessed and the role of lymphatic drainage in atherogenesis is not well understood. We develop a method to measure aortic lymphatic transport of macromolecules and show that it is impaired during atherosclerosis progression, whereas it is ameliorated during lesion regression induced by ezetimibe. Disruption of aortic lymph flow by lymphatic ligation promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and inhibits ezetimibe-induced atherosclerosis regression. Thus, progression of atherosclerotic plaques may result not only from increased entry of atherogenic factors into the arterial wall but also from reduced lymphatic clearance of these factors as a result of aortic lymph stasis. Our findings suggest that promoting lymphatic drainage might be effective for treating atherosclerosis.

scholarly journals Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces

2015 ◽  
Vol 36 (3) ◽  
pp. 576-580 ◽  
Author(s):  
Susanne J van Veluw ◽  
Geert Jan Biessels ◽  
Willem H Bouvy ◽  
Wim GM Spliet ◽  
Jaco JM Zwanenburg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Centrum Semiovale ◽  
Tissue Sections ◽  
Cortical Areas ◽  
Cerebral Amyloid

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

Perivascular (Virchow–Robin) spaces

2021 ◽  
pp. 86-89
Keyword(s):  
Blood Vessels ◽  
Shape Change ◽  
Lymphatic Drainage ◽  
Brain Regions ◽  
Mechanical Trauma ◽  
Normal Brain ◽  
Perivascular Spaces ◽  
Mr Images ◽  
Lenticulostriate Artery ◽  
The Brain

Perivascular spaces; also known as the Virchow-Robin Spaces, they are pleurally lined, interstitial fluid-filled areas that surround certain blood vessels in various organs, especially the perforating arteries in the brain, with an immunological function. Dilated perivascular spaces are divided into three types. The first of these is on the lenticulostriate artery, the second is in the cortex following the path of the medullary artery, and the third is in the midbrain. Perivascular spaces can be detected as areas of dilatation on MR images. Although a limited number of perivascular spaces can be seen in a normal brain, the increase in the number of these spaces has been associated with the incidence of various neurodegenerative diseases. Different theories have been suggested about the tendency of the perivascular spaces to expand. Current theories include mechanical trauma due to cerebrospinal fluid pulsing, elongation of penetrating blood vessels, unusual vascular permeability, and increased fluid exudation. In addition, the brain tissue atrophy that occurs with aging; It is thought to contribute to the widening of perivascular spaces by causing shrinkage of arteries, altered arterial wall permeability, obstruction of lymphatic drainage pathways and vascular demyelination. It is assumed that the clinical significance of the dilation tendencies of the perivascular spaces is based on shape change rather than size. These spaces have been mostly observed in brain regions such as corpus callosum, cingulate gyrus, dentate nucleus, substantia nigra and various arterial basins including lenticulostriate artery and mesencephalothalamic artery. In conclusion, when sections are taken on MR imaging, it is possible that perivascular spaces may be confused with microvascular diseases and some neurodegenerative changes. In addition, perivascular spaces can be seen without pathological significance. Therefore, it would be appropriate to investigate the etiological relationship by evaluating the radiological findings and clinical picture together.

scholarly journals Arterial Stiffness Is Associated With Basal Ganglia Enlarged Perivascular Spaces and Cerebral Small Vessel Disease Load

Stroke ◽  
2018 ◽  
Vol 49 (5) ◽  
pp. 1279-1281 ◽  
Author(s):  
Iolanda Riba-Llena ◽  
Joan Jiménez-Balado ◽  
Xavier Castañé ◽  
Anna Girona ◽  
Antonio López-Rueda ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Arterial Stiffness ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease

Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
Matthew Frosch ◽  
Jean-Claude Baron ◽  
Marco Pasi ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Diagnostic Accuracy ◽  
Cerebral Amyloid Angiopathy ◽  
Brain Mri ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Validation Sample ◽  
Temporal Validation ◽  
Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

Vessels Sing Their ARIAs: The Role of Vascular Amyloid in the Age of Aducanumab

Stroke ◽  
2021 ◽  
Author(s):  
Lukas Sveikata ◽  
Andreas Charidimou ◽  
Anand Viswanathan
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
High Rate ◽  
Amyloid Angiopathy ◽  
Cerebrovascular Pathology ◽  
Cerebral Amyloid

We review the implications of the recently approved aducanumab amyloid-β immunotherapy for treating Alzheimer disease with comorbid cerebral amyloid angiopathy. In clinical trials, amyloid-β immunotherapy has been associated with a high rate of amyloid-related imaging abnormalities, potentially driven by coexisting cerebral amyloid angiopathy. Therefore, immunotherapy’s efficacy in patients may be modified by coexisting cerebrovascular pathology. We discuss the contributions of cerebral amyloid angiopathy on the development of amyloid-related imaging abnormalities and propose strategies to identify cerebral amyloid angiopathy in patients considered for immunotherapy.

Abstract WP238: Atrial Fibrillation is Associated With Severe Basal Ganglia Perivascular Spaces

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Alvin S Das ◽  
Elif Gokcal ◽  
Robert W Regenhardt ◽  
Andrew Warren ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Basal Ganglia ◽  
Multiple Regression ◽  
Regression Models ◽  
Small Vessel Disease ◽  
Perivascular Spaces ◽  
Nonvalvular Atrial Fibrillation ◽  
Related Factors ◽  
Multiple Regression Models ◽  
Independent Effects

Introduction: High burdens of basal ganglia-perivascular spaces (BG-PVS) are often attributed to underlying hypertensive cerebral small vessel disease (HTN-CSVD). Although PVS are thought to arise from decreased perivascular drainage related to changes in arterial pulsatility, the contribution of pulsatility changes from nonvalvular atrial fibrillation (NVAF) has not been studied. Hypothesis: We hypothesized that NVAF patients have a higher burden of BG-PVS than HTN-CSVD patients, possibly through hemodynamic factors related to NVAF. Methods: Through an observational single-center study of consecutive stroke patients, we compared BG-EPVS severity between 136 patients with NVAF-related ischemic stroke (NVAF-IS) and 107 patients with HTN-CSVD-related intracerebral hemorrhage (HTN-ICH) without NVAF. Within the NVAF cohort, we also built multiple regression models to evaluate independent effects of NVAF-related factors on BG-PVS. All multiple regression models were adjusted for age, hypertension, sex, and neuroimaging markers of CSVD (extent of white matter hyperintensities (WMH), presence of lacunes, and cerebral microbleeds). Results: Patients with NVAF-IS were older than patients with HTN-ICH (75 + 12 vs. 64 + 13, p < 0.0001); however, there was no difference in sex between groups ( p = 0.6). Severe BG-PVS (defined as > 20 PVS in the BG) were found in 42.6% of NVAF-IS patients vs. 8.4% of HTN-ICH ( p < 0.0001). Even after multivariate adjustment, the presence of NVAF remained significantly related to BG-PVS ( p = 0.001). Within the NVAF cohort, CHA2DS2-VASc was associated with the presence of severe BG-PVS ( p = 0.003) despite controlling for other covariates. When CHA2DS2-VASc was replaced with its individual components in the same regression model, congestive heart failure (CHF, p = 0.017), WMH burden ( p = 0.009), and age ( p = 0.02) were found to be predictors of severe BG-PVS. Conclusions: Severe BG-PVS were significantly more common in NVAF patients compared to HTN-CSVD patients. NVAF-related features (CHA2DS2-VASc score) and CHF were associated with higher burdens of BG-PVS. These findings suggest that NVAF might play a role in the development of BG-PVS, conceivably through hemodynamic factors.

Abstract 56: Macrophage Reverse Cholesterol Transport in Mice Relies on The Lymphatic Vasculature

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Catherine Martel ◽  
Wenjun Li ◽  
Brian Fulp ◽  
Andrew Platt ◽  
Emmanuel L Gautier ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Aortic Wall ◽  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Fecal Excretion ◽  
Lymphatic Transport ◽  
Cholesterol Transport ◽  
Transport Function ◽  
Peripheral Tissues ◽  
Lymphatic Vasculature

Reverse cholesterol transport (RCT) refers to mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used two models of disrupted lymphatic drainage from skin -one surgical and the other genetic- to quantitatively track RCT following injection of [3H]cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analogue (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aorta of donor atherosclerotic apoE-/- mice with [2H]6-labeled cholesterol and surgically transplanting these aortas into recipient apoE-/- mice that were treated with anti-VEGFR3 mAb to block lymphatic regrowth or with control mAb to allow such regrowth. [2H]-Cholesterol was retained in aortas of anti-VEGFR3 treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. Therefore, supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

Abstract WP344: Basal Ganglia Atrophy in Cerebral Amyloid Angiopathy

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Panagiotis Fotiadis ◽  
Marco Pasi ◽  
Andreas Charidimou ◽  
Myung J Lee ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

scholarly journals Advances in cerebral amyloid angiopathy imaging

2019 ◽  
Vol 12 ◽  
pp. 175628641984411 ◽  
Author(s):  
Szu-Ju Chen ◽  
Hsin-Hsi Tsai ◽  
Li-Kai Tsai ◽  
Sung-Chun Tang ◽  
Bo-Chin Lee ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Imaging Techniques ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Clinical Aspects ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Imaging Studies ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer’s disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects.

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