Abstract 140: Vascular Structure in Brain: Lack of Small Vessel Recovery Following Hypertension

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Gary Baumbach ◽  
Rasna Sabharwal ◽  
Thomas Gerhold ◽  
Mark Chapleau ◽  
Frank M Faraci
Keyword(s):  
Vessel Wall ◽  
Small Vessel Disease ◽  
Recovery Period ◽  
Small Vessel ◽  
Internal Diameter ◽  
Vascular Structure ◽  
Ang Ii ◽  
Vascular Events ◽  
Cerebral Arterioles ◽  
The Impact

Vascular remodeling is a feature of small vessel disease (SVD), predictive of vascular events, brain injury, and cognitive decline. Hypertension alters vascular structure including diameter and cross-sectional area (CSA) of the vessel wall. While effects of hypertension on large arteries have been studied relatively widely, detailed quantification, including recovery from hypertension in microvessels, is rare. Previously, angiotensin II (Ang II)-dependent hypertension produced increased CSA but reduced internal diameter (ID) of cerebral arterioles (inward remodeling) in brain. Because cerebral arterioles are targets of SVD, we examined the hypothesis that brain microvessels can recover from hypertension after return of mean arterial pressure (MAP) to normal levels. MAP was measured using radiotelemetry in adult male C57BL6J mice at baseline, during infusion of vehicle or Ang II (1.4 mg/kg per day using osmotic mini-pumps) for 28 days, and during a 28 day recovery period (n=5 in each group). Prior to treatment, MAP was similar in both groups, with MAP remaining stable in vehicle treated mice. With Ang II treatment, MAP began to rise on day 3, steadily increasing until day 28. On day 30, MAP began to decrease, reaching levels seen with vehicle on days 46-47. In anesthetized mice, we measured pressure, diameter, and CSA of the vessel wall in maximally dilated arterioles (baseline diameter of 62±3 microns) at 1, 3, 7, 14, 28, and 56 days after pump implantation (n=7-9 in each group). At day 1, ID and CSA were similar in both groups. With vehicle, there was no significant change in CSA or ID at any time point. With Ang II, CSA increased at day 7 and was maintained at days 14 and 28 (P=0.023). ID did not change at day 3 or 7, but was reduced (by ~15%, P=0.011) at 14 and 28 days. During recovery (day 56), CSA returned 63% of the way to normal (compared to vehicle), while ID remained at day 14 and 28 values. In conclusion, CSA changed rapidly during hypertension onset and largely recovered with a reduction in MAP. Inward remodeling developed slowly and did not recover after return of MAP to control levels. The lack of recovery after hypertension has implications for the impact of SVD including hypoperfusion, impaired vasodilation, and augmented injury during ischemia.

scholarly journals Cerebral Small Vessel Disease

2020 ◽  
Vol 21 (24) ◽  
pp. 9729
Author(s):  
Jakub Litak ◽  
Marek Mazurek ◽  
Bartłomiej Kulesza ◽  
Paweł Szmygin ◽  
Joanna Litak ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Vessels ◽  
Small Vessel ◽  
Epithelial Layer ◽  
Small Arteries ◽  
Vessel Disease ◽  
The Impact ◽  
Cerebral Small Vessel Diseases

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger’s disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.

Abstract T MP35: Frequency, Risk Factors, and Impact of Coexistent Small Vessel Disease in the SAMMPRIS Trial

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hyung-Min Kwon ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Stroke Recurrence ◽  
Logrank Test ◽  
Exact Test ◽  
Vessel Disease ◽  
Atherosclerotic Stenosis ◽  
The Impact

Background: Intracranial atherosclerotic stenosis (ICAS) and small vessel disease (SVD) may coexist. We investigated the frequency and risk factors for SVD in SAMMPRIS patients and the impact of SVD on stroke recurrence in the medical arm of the trial. Methods: Of 451 patients enrolled in SAMMPRIS, 313 had baseline brain MRIs read centrally for SVD. SVD was defined by any of the following: old lacunar infarction, Fazekas score of 2-3 for white matter hyperintensities, or microbleeds. We compared risk factors in patients with vs. without SVD using Fisher’s exact test (for percentages), independent groups t test (for means) or Wilcoxon rank sum test (for medians), and compared the survival curves of patients with vs. without SVD in the medical arm for ischemic stroke in the territory of the stenotic artery and any ischemic stroke using the logrank test. Results: Of the 313 patients, 161 (51.4%) had SVD on the baseline MRI. Variables that were significantly (p<0.05) higher in patients with SVD were age, diabetes, lipid disorder, baseline SBP, coronary disease, and old infarct in the territory. The Kaplan-Meier curves in the figure show that patients with SVD were at significantly higher risk of any ischemic stroke (p = 0.048) but not stroke in the territory (p = 0.10) compared with patients without SVD. Conclusion: SVD in patients with ICAS is common, especially in patients who are older, diabetic, hyperlipidemic, and have higher SBP. Patients with ICAS and coexistent SVD are at higher risk of any ischemic stroke but may not be at higher risk for stroke in the territory.

Small vessel disease

2020 ◽  
pp. 203-212
Author(s):  
Fergus N Doubal ◽  
Anna Poggesi ◽  
Leonardo Pantoni ◽  
Joanna M Wardlaw
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Intrinsic Disorder ◽  
Small Vessel ◽  
Imaging Features ◽  
World Region ◽  
Vessel Disease ◽  
Cerebral Arterioles ◽  
The Brain ◽  
Review Current

‘Small vessel disease’ describes a combination of neuroradiological and clinical features that are due to an intrinsic disorder of the small cerebral arterioles, capillaries, and venules in varying proportions. It is very common, usually sporadic, although rare monogenic forms are well described. The commonest presentations are with stroke or cognitive impairment. The cause of the small vessel abnormalities in the sporadic form is not well understood and the brain damage is generally attributed to ischaemia secondary to the vessel abnormality. However, evidence for altered microvessel function and blood brain barrier failure is accumulating. The commonest risk factors are increasing age, hypertension, smoking, and diabetes, but environmental and lifestyle factors are also important although poorly understood. Whether the imaging features or incidence of small vessel-related stroke or dementia vary by world region is unknown. We review current knowledge on presentation, aetiology, incidence, and prevalence of sporadic small vessel disease.

scholarly journals Contributions of Aging to Cerebral Small Vessel Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 275-295 ◽  
Author(s):  
T. Michael De Silva ◽  
Frank M. Faraci
Keyword(s):  
Recent Progress ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Brain Health ◽  
Vessel Disease ◽  
Age Related ◽  
The Face ◽  
Basic Biology ◽  
The Impact

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Underlying phenotypes and mechanisms are multifactorial, with no specific treatments at this time. Despite consequences that are already considerable, the impact of SVD is predicted to increase substantially with the growing aging population. In the face of this health challenge, the basic biology, pathogenesis, and determinants of SVD are poorly defined. This review summarizes recent progress and concepts in this area, highlighting key findings and some major unanswered questions. We focus on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.

scholarly journals Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease

2020 ◽  
Vol 5 (3) ◽  
pp. 297-308
Author(s):  
Joanna Wardlaw ◽  
Philip M W Bath ◽  
Fergus Doubal ◽  
Anna Heye ◽  
Nikola Sprigg ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Large Trial ◽  
Intervention Trial ◽  
Vascular Events ◽  
Phase 3 ◽  
Full Dose ◽  
Vessel Disease

Background Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial. Methods and design LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability. Summary LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.

[P2-219]: INFLAMMATION MEDIATES THE IMPACT OF SMALL-VESSEL DISEASE ON COGNITION IN ALZHEIMER'S DISEASE: EVIDENCE FROM A MULTIMODAL STRATIFIED COHORT STUDY

2017 ◽  
Vol 13 (7S_Part_14) ◽  
pp. P693-P694
Author(s):  
Di Yu ◽  
Joel Ramirez ◽  
Hugo Cogo-Moreira ◽  
Gustavo Scola ◽  
Pak Cheung Chan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cohort Study ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
The Impact

scholarly journals Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic

2021 ◽  
Vol 13 ◽  
Author(s):  
Yangyi Fan ◽  
Ming Shen ◽  
Yang Huo ◽  
Xuguang Gao ◽  
Chun Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cognitive Status ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Vessel Disease ◽  
Mri Features ◽  
The Impact

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P &lt; 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA &lt; 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA &lt; 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.

Lesion location and cognitive impact of cerebral small vessel disease

2017 ◽  
Vol 131 (8) ◽  
pp. 715-728 ◽  
Author(s):  
J. Matthijs Biesbroek ◽  
Nick A. Weaver ◽  
Geert Jan Biessels
Keyword(s):  
Image Analysis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Case Series ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Lesion Location ◽  
Vessel Disease ◽  
The Impact

Cerebral small vessel disease (SVD) is an important cause of cognitive impairment. Important MRI manifestations of SVD include white matter hyperintensities (WMH) and lacunes. This narrative review addresses the role of anatomical lesion location in the impact of SVD on cognition, integrating findings from early autopsy studies with emerging findings from recent studies with advanced image analysis techniques. Early autopsy and imaging studies of small case series indicate that single lacunar infarcts in, for example the thalamus, caudate nucleus or internal capsule can cause marked cognitive impairment. However, the findings of such case studies may not be generalizable. Emerging location-based image analysis approaches are now being applied to large cohorts. Recent studies show that WMH burden in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation (ATR), is more relevant in explaining variance in cognitive functioning than global WMH volume. These findings suggest that the future diagnostic work-up of memory clinic patients could potentially be improved by shifting from a global assessment of WMH and lacune burden towards a quantitative assessment of lesion volumes within strategic brain regions. In this review, a summary of currently known strategic regions for SVD-related cognitive impairment is provided, highlighting recent technical developments in SVD research. The potential and challenges of location-based approaches for diagnostic purposes in clinical practice are discussed, along with their potential prognostic and therapeutic applications.

scholarly journals A Mouse Model of Small-Vessel Disease that Produces Brain-Wide-Identified Microocclusions and Regionally Selective Neuronal Injury

2015 ◽  
Vol 35 (5) ◽  
pp. 734-738 ◽  
Author(s):  
Gergely Silasi ◽  
Jennifer She ◽  
Jamie D Boyd ◽  
Songchao Xue ◽  
Timothy H Murphy
Keyword(s):  
Mouse Model ◽  
Structural Damage ◽  
Small Vessel Disease ◽  
Neuronal Damage ◽  
Cell Loss ◽  
Small Vessel ◽  
Neuronal Structure ◽  
Produce Cell ◽  
Vessel Disease ◽  
The Impact

We developed a mouse model of small-vessel disease where occlusions are produced through endovascular injection of fluorescent microspheres that target ~12 μm diameter penetrating arterioles and can be localized in histology. Using Thy1-GFP transgenic mice, we visualized the impact of microocclusions on neuronal structure. Microocclusions in the hippocampus produce cell loss or neuronal atrophy (~7% of lodged microspheres led to microinfarcts), while axons within white matter tracts, as well as the striatum and thalamus became blebbed or disrupted. Although the neocortex contained more occlusions than other structures, labeled layer 5 neurons were relatively resistant to structural damage, with <2% of the lodged microspheres producing obvious neuronal damage.

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