Brain & cognition: 9 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational Study
This is a study protocol (not results) for CRUCIAL, a consortium of four observational cohort studies investigating whether microvascular rarefaction \u2014 loss of perfused and structural microvessels \u2014 contributes to vascular cognitive impairment from cerebral small vessel disease and to heart failure with preserved ejection fraction. Investigators plan to compare advanced brain and cardiac MRI measures of microvascular density with easier surrogate measures, including sublingual capillary assessment, retinal optical coherence tomography angiography, and RNA from circulating extracellular vesicles. In the aortic stenosis surgical cohort, myocardial biopsies will provide histological validation of microvascular density.
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Published paper
Cerebrovascular glycocalyx damage and microcirculation impairment in patients with temporal lobe epilepsy
Researchers used intraoperative sidestream dark-field video microscopy (GlycoCheck) to measure the endothelial glycocalyx and capillary blood flow directly on the exposed brain surface of 15 patients undergoing surgery for drug-resistant temporal lobe epilepsy and 15 non-epileptic surgical controls. Cortical perfused boundary region (PBR), an indirect marker of glycocalyx damage, was roughly twice as high in epilepsy patients, and their capillary recruitment capacity was markedly reduced. In vivo vessel surface area correlated strongly with ex vivo lectin-stained vessel area in the same resected tissue.
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Published paper
Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study
This is a published study protocol (no results yet) for CRUCIAL, a multicenter observational program investigating whether microvascular rarefaction - loss of perfused small vessels - is a shared mechanism in vascular cognitive impairment and heart failure with preserved ejection fraction. Participants across four cohorts (75 VCI, 60 HFpEF, 60 aortic stenosis, 200 aging controls) undergo advanced brain and cardiac MRI, cognitive testing, echocardiography, retinal OCT angiography, sublingual videomicroscopy with the GlycoCheck system, blood biomarkers, and (in the surgical cohort) myocardial biopsy. The aim is to validate cheaper non-invasive surrogate markers of microvascular density against imaging and histology.
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Published paper
Microvascular rarefaction in patients with cerebrovascular events
This prospective observational study used sublingual sidestream darkfield videomicroscopy to assess microcirculation in 21 patients within 24 hours of an acute stroke or transient ischemic attack, with repeat measurements on day 3 and after one week, compared with age- and sex-matched healthy controls. Patients showed substantially lower capillary density than controls, and the perfused boundary region (an inverse marker of glycocalyx thickness) correlated strongly with red blood cell filling of capillaries. The authors conclude that cerebrovascular events are accompanied by measurable systemic microvascular changes detectable under the tongue.
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Published paper
Persistent capillary rarefication in long COVID syndrome
This prospective observational study used sublingual sidestream dark-field videomicroscopy with GlycoCheck software to compare microvascular structure and function in 27 long COVID patients, 15 healthy controls, and 16 historical critically ill COVID-19 patients. Long COVID patients showed a marked loss of the smallest capillaries and impaired capillary recruitment a median of ~18 months after infection, while glycocalyx thickness (PBR) was similar to healthy controls. The authors conclude that COVID-19 may leave persistent capillary rarefication, though the design cannot establish causality with symptoms.
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Published paper
Uncoupling of Microvascular Blood Flow and Capillary Density in Vascular Cognitive Impairment
Researchers used sublingual video microscopy (GlycoCheck system) to compare how the smallest blood vessels respond to spontaneous changes in blood flow in 15 men with vascular cognitive impairment from cerebral small vessel disease and 15 male controls. In healthy controls, the number of red-cell-perfused capillaries rose as feed vessel flow rose, whereas in patients with cognitive impairment it did not. The authors interpret this as an uncoupling of microvascular flow from perfused capillary density, which could limit oxygen and nutrient exchange when metabolic demand increases.
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Published paper
In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report
This technical report describes the first in vivo measurement of the human cerebral microcirculation and its endothelial glycocalyx using sidestream dark-field (SDF) imaging with GlycoCheck software during brain surgery. Measurements were taken sublingually (as a reference), and from cortical and hippocampal surfaces in five epilepsy surgery patients, with a sterile slipcover over the camera required in the operating field. Vessel density and perfused boundary region (PBR) showed broadly similar patterns across the three sites, but the sterile slipcover itself altered the measured values.
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Published paper
Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.
This is a published study protocol (no results) for a multicenter prospective case-control study in the Netherlands that plans to image the endothelial glycocalyx intraoperatively in the human brain. Using sidestream dark-field video microscopy with GlycoCheck software, investigators will measure the perfused boundary region (PBR) and perfused diameter in sublingual, cortical, and (in epilepsy patients only) hippocampal microvessels. The hypothesis is that cerebrovascular glycocalyx thickness is reduced in temporal lobe epilepsy compared with controls, potentially linking glycocalyx damage to blood-brain barrier leakage and seizure susceptibility.
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Published paper
Sublingual microvascular glycocalyx dimensions in lacunar stroke patients
Researchers used sidestream dark-field imaging of the sublingual microcirculation to estimate glycocalyx thickness (via the perfused boundary region, PBR) in 31 patients with lacunar stroke and 19 healthy controls. Overall, PBR did not differ between stroke patients and controls, but the subgroup of stroke patients who also had white matter lesions on MRI showed a significantly larger PBR, suggesting a thinner or more permeable glycocalyx. The authors interpret this as evidence of impaired endothelial barrier function in more extensive cerebral small vessel disease.
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