Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

Latest research in nootropic therapy of patients with chronic cerebral circulation insufficiency.

OBJECTIVE: Aim: To analyze latest research on the usage of choline alfoscerate and ethylmethylhydroxypyridine succinate (EMHPS) as nootropic therapy for patients with chronic cerebral circulation insufficiency (CCCI). PATIENTS AND METHODS: Materials and Methods: Bibliosemantic, comparative and system analysis methods were used in the study. The proposed recommendations are developed on the basis of the analysis of modern literature, the results of randomized studies and meta-analyses, authoritative studies devoted to the study of the CCCI problem. CONCLUSION: Conclusions: The combination of EMHPS with choline alfoscerate for the complex treatment of CCCI and associated syndromes improves the functions of the endothelium, leads to asthenic syndrome, indicators of stress, depression and anxiety decreasing has a positive effect on the cognitive impairment and complications' progress reduction.

Brain-specific biomarkers in urine as a non-invasive approach to monitor neuronal and glial damage.

BACKGROUND AND PURPOSE: This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and total tau (t-tau) in urine of patients with acute cerebral damage. METHODS: Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single-molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin-creatinine ratio (ACR); biomarker-creatinine ratios were calculated for correction of urine dilution. RESULTS: Ninety-three urine-serum pairs in the target group and 10 urine-serum pairs in the control group were measured. The mean absolute concentration ± standard deviation in urine of the target and control groups were 184.7 ± 362.4 pg/ml and 27.3 ± 24.1 pg/ml for GFAP (r = 0.3 [Wilcoxon effect size], p = 0.007), 17.5 ± 38.6 pg/ml and 0.9 ± 0.3 pg/ml for NfL (r = 0.4, p < 0.005), 320.2 ± 443.3 pg/ml and 109.6 ± 116.8 pg/ml for UCH-L1 (r = 0.26, p = 0.014), and 219.5 ± 255.8 pg/ml and 21.1 ± 27.1 pg/ml for t-tau (r = 0.37, p < 0.005), respectively, whereas biomarker-creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t-tau (r = 0.32, p < 0.01). In patients with intact glomerular barrier (ACR < 30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation-coefficient], p < 0.005). CONCLUSION: All four investigated biomarkers could be measured in urine, with NfL and t-tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.

MINE-BLAST TRAUMA AS A FACTOR IN THE EARLY DEVELOPMENT OF VASCULAR DISEASES OF THE BRAIN.

OBJECTIVE: The aim of this study is to investigate the state of bulbar conjunctival vessels, rheological properties of blood, catecholamines (adrenaline, norepinephrine), lipid metabolism, alkaline proteins of blood serum in patients with consequences of mild combat traumatic brain injury. PATIENTS AND METHODS: Materials and methods: 76 individuals aged 28 to 41 years were examined. The duration of the injury lasted from 2 to 4 years. The control group consisted of 28 individuals aged 45 to 49 years with primary cerebral atherosclerosis and manifestations of cerebral circulation disorders. The state of the bulbar conjunctiva vessels and blood circulation was studied using a slit lamp SHCHL-2B at 40-fold magnification. Rheological parameters, lipid metabolism, serum alkaline proteins, total catecholamines were studied according to generally accepted methods. RESULTS: Results: Changes in the vessels of the bulbar conjunctiva (stage II-III) were detected in 76% of the subjects, indicating the formation of cerebral vascular pathology, and in 87% of patients with initial cerebral atherosclerosis. The analysis of lipid metabolism showed significantly (p<0.05) increased data on all studied parameters (cholesterol, high-density lipoprotein, ß-lipoprotein, atherogenic index), both in patients with aftereffects of mild combat traumatic brain injury and in patients with initial cerebral atherosclerosis. An increase in alkaline proteins indices we detected in 62% of patients with aftereffects of mild combat cerebral trauma and in 55% of patients with initial cerebral atherosclerosis. At the same time, there was an increase in total catecholamines in the erythrocytes of patients with combat head injury. An increase in fibrinogen was noted in both groups, but in the group with initial cerebral atherosclerosis it was more pronounced. CONCLUSION: Conclusions: Combat traumatic brain injury contributes to the early formation of cerebral atherosclerosis and cerebral circulation disorders in this category of patients. The examination methods we have studied should be included in the survey plan for these patients. They are important not only for diagnosis, but also for improving treatment and preventing vascular disasters.

[The awareness of primary health care physicians about methods of evaluation of risks of stroke].

The assessment of prevalence of acute cerebral circulation disorders in persons with arterial hypertension, together with study of awareness of primary health care physicians about methods of assessing risk of stroke, allows to judge effectiveness of measures preventing acute cerebral circulation disorders and to outline further ways preventing cerebrovascular complications of hypertension.The purpose of study was to investigate morbidity of acute cerebral circulation disorders and awareness of primary care physicians about clinical and instrumental methods assessing risk of stroke in persons with arterial hypertension.Materials and methods included official statistical materials on morbidity of intracerebral bleeding and cerebral infarction in population of Russia, the Chelyabinsk Oblast in 2008-2020, totals of survey of internists and emergency physicians in six regions of Russia.It was established that morbidity of intracerebral bleeding and cerebral infarction in 2008-2020 in the Chelyabinsk Oblast has not changed, while morbidity of intracerebral bleeding and brain infarction in Russia significantly (p.

Use of real-time phase-contrast MRI to quantify the effect of spontaneous breathing on the cerebral arteries.

Quantification of the effect of breathing on the cerebral circulation provides a better mechanistic understanding of the brain's circulatory system and is important in the early diagnosis of certain neurological diseases. However, conventional cine phase-contrast (CINE-PC) MRI cannot be used in this field of study because it only provides an average cardiac cycle flow curve reconstructed from multiple cardiac cycles. Unlike CINE-PC, phase-contrast echo-planar imaging (EPI-PC) can be used to quantify the blood flow rate in "real-time" and thus assess the effect of breathing on blood flow. Here, we first used post-processing software (developed in-house) to determine the feasibility of quantifying cerebral arterial blood flow with EPI-PC (relative to CINE-PC) in 16 participants. In a second step, we developed a new time-domain method for quantifying the intensity and the phase shift of the effects of breathing on the mean flow rate, stroke volume, cardiac period and amplitude of cerebral blood flow (in 10 participants). Our results showed that EPI-PC can quantify cerebral arterial blood flow rate with much the same degree of accuracy as CINE-PC but is more strongly influenced by differences in magnetic susceptibility. We found that breathing affected the mean flow rate, stroke volume and cardiac period of cerebral arterial blood flow.

Defining a role of NADPH oxidase in myogenic tone development.

OBJECTIVE: The myogenic response sets the foundation for blood flow control. Recent findings suggest a role for G protein-coupled receptors (GPCR) and signaling pathways tied to the generation of reactive oxygen species (ROS). In this regard, this study ascertained the impact of NADPH oxidase (Nox) on myogenic tone in rat cerebral resistance arteries. METHODS: The study employed real-time qPCR (RT-qPCR), pressure myography, and immunohistochemistry. RESULTS: Gq blockade abolished myogenic tone in rat cerebral arteries, linking GPCR to mechanosensation. Subsequent work revealed that general (TEMPOL) and mitochondrial specific (MitoTEMPO) ROS scavengers had little impact on myogenic tone, whereas apocynin, a broad spectrum Nox inhibitor, initiated transient dilation. RT-qPCR revealed Nox1 and Nox2 mRNA expression in smooth muscle cells. Pressure myography defined Nox1 rather than Nox2 is facilitating myogenic tone. We rationalized that Nox1-generated ROS was initiating this response by impairing the ability of the CaV 3.2 channel to elicit negative feedback via BKCa . This hypothesis was confirmed in functional experiments. The proximity ligation assay further revealed that Nox1 and CaV 3.2 colocalize within 40 nm of one another. CONCLUSIONS: Our data highlight that vascular pressurization augments Nox1 activity and ensuing ROS production facilitates myogenic tone by limiting Ca2+ influx via CaV 3.2.

Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia-Occam's razor or Hickam's dictum: a case report.

BACKGROUND: Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves' disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. CASE PRESENTATION: A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. CONCLUSIONS: With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.

Non-parametric deconvolution using Bézier curves for quantification of cerebral perfusion in dynamic susceptibility contrast MRI.

OBJECTIVE: Deconvolution is an ill-posed inverse problem that tends to yield non-physiological residue functions R(t) in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). In this study, the use of Bézier curves is proposed for obtaining physiologically reasonable residue functions in perfusion MRI. MATERIALS AND METHODS: Cubic Bézier curves were employed, ensuring R(0) = 1, bounded-input, bounded-output stability and a non-negative monotonically decreasing solution, resulting in 5 parameters to be optimized. Bézier deconvolution (BzD), implemented in a Bayesian framework, was tested by simulation under realistic conditions, including effects of arterial delay and dispersion. BzD was also applied to DSC-MRI data from a healthy volunteer. RESULTS: Bézier deconvolution showed robustness to different underlying residue function shapes. Accurate perfusion estimates were observed, except for boxcar residue functions at low signal-to-noise ratio. BzD involving corrections for delay, dispersion, and delay with dispersion generally returned accurate results, except for some degree of cerebral blood flow (CBF) overestimation at low levels of each effect. Maps of mean transit time and delay were markedly different between BzD and block-circulant singular value decomposition (oSVD) deconvolution. DISCUSSION: A novel DSC-MRI deconvolution method based on Bézier curves was implemented and evaluated. BzD produced physiologically plausible impulse response, without spurious oscillations, with generally less CBF underestimation than oSVD.

A prospective observational study of emboli exposure in open versus closed chamber cardiac surgery.

OBJECTIVE: Exposure to cerebral emboli is ubiquitous and may be harmful in cardiac surgery utilizing cardiopulmonary bypass. This was a prospective observational study aiming to compare emboli exposure in closed-chamber with open-chamber cardiac surgery, distinguish particulate from gaseous emboli and examine cerebral laterality in distribution. METHODS: Forty patients underwent either closed-chamber procedures (n = 20) or open-chamber procedures (n = 20). Emboli (gaseous and solid) were detected using transcranial Doppler in both middle cerebral arteries in two monitoring phases: 1, initiation of bypass to the removal of the aortic cross-clamp; and 2, removal of aortic cross-clamp to 20 minutes after venous decannulation. RESULTS: Total (median (interquartile range)) emboli counts (both phases) were 898 (499-1366) and 2617 (1007-5847) in closed-chamber and open-chamber surgeries, respectively. The vast majority were gaseous; median 794 (closed-chamber surgery) and 2240 (open-chamber surgery). When normalized for duration, there was no difference between emboli exposures in closed-chamber and open-chamber surgery in phase 1: 6.8 (3.6-15.2) versus 6.4 (2.0-18.1) emboli per minute, respectively. In phase 2, closed-chamber surgery cases were exposed to markedly fewer emboli than open-chamber surgery cases: 9.6 (5.1-14.9) versus 43.3 (19.7-60.3) emboli per minute, respectively. More emboli (total) passed into the right cerebral circulation: 985 (397-2422) right versus 376 (198-769) left. CONCLUSIONS: Patients undergoing open-chamber surgery are exposed to considerably higher numbers of cerebral arterial emboli after removal of the aortic cross-clamp than those undergoing closed-chamber surgery, and more emboli enter the right middle cerebral artery than the left. These results may help inform the evaluation of the pathophysiological impact of emboli exposure.

FEATURES OF CEREBRAL HEMODYNAMICS IN PATIENTS AFTER STROKE DEPENDING ON THE VARIABILITY OF BLOOD PRESSURE AND THEIR QUALITY OF LIFE.

OBJECTIVE: The aim: To study cerebral hemodynamics in patients after ischemic stroke (IS) depending on the variability of blood pressure (BP) and to assess the quality of life (QOL). PATIENTS AND METHODS: Materials and methods: The study included 90 patients of SIS «RSCPC¼ SAD aged 33 to 72 years: The 1st (main) group consisted of 30 patients with ischemic stroke (IS) on the background of hypertension (HTN) with mild neurological deficits; 2nd - 30 patients who have been suffering from HTN for more than 10 years and have manifestations of dyscirculatory encephalopathy of I-II stage.; 3rd group - 30 patients who did not suffer from HTN. RESULTS: Results: Variability of blood pressure in patients with ischemic stroke with mild neurological deficits on the background of hypertension (hypertension) did not differ significantly from that in patients with hypertension with more than 10 years of experience, but their cerebral blood flow rate was significantly lower. Neurological functions, cognitive and psycho-emotional statuses and, as a consequence, quality of life were also significantly worse in patients after stroke. CONCLUSION: Conclusions: cerebral disorders and quality of life in patients after stroke are associated with decreased cerebral blood flow, regardless of the variability of blood pressure.

[Mathematical modeling of high-flow extra-intracranial bypass in the treatment of a complex cerebral aneurysm]. / Matematicheskoe modelirovanie obkhodnogo vysokopotochnogo ekstra-intrakranial'nogo shuntirovaniya pri lechenii slozhnoi tserebral'noi anevrizmy.

BACKGROUND: Intracranial aneurysms (IAs) pose a high risk of spontaneous subarachnoid hemorrhage. In the most complex cases, the only way to exclude the aneurysm from the circulation is to perform a high-flow extracranial-to-intracranial bypass, thus creating a new bloodstream. This avoids severe ischemic complications; however, it requires careful consideration of individual anatomy and hemodynamic parameters. Computational fluid dynamics (CFD) can be of great help in planning such a surgery by creating 3D patient-specific models of cerebral circulation. OBJECTIVE: Assessment of the perspectivity of high-flow extracranial-to-intracranial bypass planning using computational modeling. MATERIAL AND METHODS: In this research work, we have applied the CFD methods to a patient with a giant thrombosed IA of the internal carotid artery (ICA). Preoperative CTA images and Gamma Multivox workstation were used to create a 3D model with current geometry and three additional models: Normal anatomy (no IA), Occlusion (with ligated ICA), Virtual bypass (with bypass and ligated ICA). The postoperative data were also available. Boundary conditions were based on PC-MRI measurements. Calculation of hemodynamics was conducted with a finite element package ANSYS Workbench 19. RESULTS: The results demonstrated an increase in the blood flow on the affected side by more than 70% after the virtual surgery and uniformity of flow distribution between the affected and contralateral sides, indicating that the treatment is likely to be efficient. Later, postoperative data confirmed that. CONCLUSION: The study showed that virtual preoperative CFD modeling could significantly simplify and improve surgical planning.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries: role of oxidative stress.

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-week old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at Δ100 mmHg, whereas l-NAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol + l-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.NEW & NOTEWORTHY The AT1R blockade impaired the endothelium-dependent, both flow- and acetylcholine-induced dilations of MCA by decreasing vascular NO production and increasing the level of vascular and systemic oxidative stress, whereas it mildly influenced the vascular wall inflammatory phenotype, but had no effect on the systemic inflammatory response. Our data provide functional and molecular evidence for an important role of AT1 receptor activation in physiological conditions, suggesting that AT1 receptors have multiple biological functions.

Mathematical synthesis of the cortical circulation for the whole mouse brain-part II: Microcirculatory closure.

Recent advancements in multiphoton imaging and vascular reconstruction algorithms have increased the amount of data on cerebrovascular circulation for statistical analysis and hemodynamic simulations. Experimental observations offer fundamental insights into capillary network topology but mainly within a narrow field of view typically spanning a small fraction of the cortical surface (less than 2%). In contrast, larger-resolution imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have whole-brain coverage but capture only larger blood vessels, overlooking the microscopic capillary bed. To integrate data acquired at multiple length scales with different neuroimaging modalities and to reconcile brain-wide macroscale information with microscale multiphoton data, we developed a method for synthesizing hemodynamically equivalent vascular networks for the entire cerebral circulation. This computational approach is intended to aid in the quantification of patterns of cerebral blood flow and metabolism for the entire brain. In part I, we described the mathematical framework for image-guided generation of synthetic vascular networks covering the large cerebral arteries from the circle of Willis through the pial surface network leading back to the venous sinuses. Here in part II, we introduce novel procedures for creating microcirculatory closure that mimics a realistic capillary bed. We demonstrate our capability to synthesize synthetic vascular networks whose morphometrics match empirical network graphs from three independent state-of-the-art imaging laboratories using different image acquisition and reconstruction protocols. We also successfully synthesized twelve vascular networks of a complete mouse brain hemisphere suitable for performing whole-brain blood flow simulations. Synthetic arterial and venous networks with microvascular closure allow whole-brain hemodynamic predictions. Simulations across all length scales will potentially illuminate organ-wide supply and metabolic functions that are inaccessible to models reconstructed from image data with limited spatial coverage.

Plasma brain-derived neurotrophic factor and dynamic cerebral autoregulation in acute response to glycemic control following breakfast in young men.

We examined the acute impact of both low- and high-glycemic index (GI) breakfasts on plasma brain-derived neurotrophic factor (BDNF) and dynamic cerebral autoregulation (dCA) compared with breakfast omission. Ten healthy men (age 24 ± 1 yr) performed three trials in a randomized crossover order; omission and Low-GI (GI = 40) and High-GI (GI = 71) breakfast conditions. Middle cerebral artery velocity (transcranial Doppler ultrasonography) and arterial pressure (finger photoplethysmography) were continuously measured for 5 min before and 120 min following breakfast consumption to determine dCA using transfer function analysis. After these measurements of dCA, venous blood samples for the assessment of plasma BDNF were obtained. Moreover, blood glucose was measured before breakfast and every 30 min thereafter. The area under the curve of 2 h postprandial blood glucose in the High-GI trial was higher than the Low-GI trial (P < 0.01). The GI of the breakfast did not affect BDNF. In addition, both very-low (VLF) and low-frequency (LF) transfer function phase or gains were not changed during the omission trial. In contrast, LF gain (High-GI P < 0.05) and normalized gain (Low-GI P < 0.05) were decreased by both GI trials, while a decrease in VLF phase was observed in only the High-GI trial (P < 0.05). These findings indicate that breakfast consumption augmented dCA in the LF range but High-GI breakfast attenuated cerebral blood flow regulation against slow change (i.e., the VLF range) in arterial pressure. Thus we propose that breakfast and glycemic control may be an important strategy to optimize cerebrovascular health.

Can Myogenic Tone Protect Endothelial Function? Integrating Myogenic Activation and Dilator Reactivity for Cerebral Resistance Arteries in Metabolic Disease.

The obese Zucker rat (OZR) manifests multiple risk factors for impaired cerebrovascular function, including hypertension and insulin resistance although how they combine to produce integrated vascular function is unclear. As studies have suggested that myogenic activation (MA) severity for middle cerebral arteries (MCAs) may be proportional to hypertension severity, we hypothesized that MA will negatively correlate with dilator reactivity in OZR. MA of MCA from OZR was divided into low, medium, and high based on the slope of MA, while MCA reactivity and vascular metabolite bioavailability were assessed in all groups. Endothelium-dependent dilation of MCA in OZR was attenuated and correlated with the MA slope. Treatment of OZR MCA with TEMPOL (antioxidant) improved dilation in low or medium MA groups, but had less impact on high MA. Alternatively, treatment with gadolinium to normalize MA in OZR had reduced impact on dilator reactivity in MCA from low and medium MA groups, but improved responses in the high group. Treatment with both agents resulted in dilator responses that were comparable across all groups. These results suggest that, under conditions with stronger MA, endothelial function may receive some protection despite the environment, potentially from the ability of MCA to reduce wall tension despite increased pressure.

Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Impact of Head-of-Bed Posture on Brain Oxygenation in Patients with Acute Brain Injury: A Prospective Cohort Study.

BACKGROUND: Therapeutic head positioning plays a role in the management of patients with acute brain injury. Although intracranial pressure (ICP) is typically lower in an upright posture than in a flat position, limited data exist concerning the effect of upright positioning on brain oxygenation and circulation. We sought to determine the impact of supine (0°) and semirecumbent (15° and 30°) postures on ICP, brain oxygenation, and brain circulation. METHODS: An observational cohort study was conducted between February 2012 and September 2015. Twenty-three patients with severe acute brain injury were successively observed at head elevations of 30°, 15°, and 0°. Postural-induced changes in ICP, cerebral perfusion pressure, brain tissue oxygenation pressure, and transcranial Doppler findings were simultaneously measured during three repeated experiments: 24 h after admission to the intensive care unit (exp1), 24 h later (exp2), and 96 h later (exp3). Cerebral perfusion pressure, arterial blood gases, hemoglobin content, and body temperature remained unchanged during the three experiments. RESULTS: Using linear random-slope mixed models, we found that during the early phase of acute brain injury (exp1), lowering the head posture from 30° to 15°, and then to 0°, was associated with a gradual mean ICP increase of 2.6 mm Hg (1.4-3.7 mm Hg; P < 0.001); and from 30° to 0°, an increase of 7.4 mm Hg (6.3-8.6 mm Hg; P < 0.001). Furthermore, brain tissue oxygenation pressure and mean blood flow velocity improved when the head posture was lowered from 30° to 0° by 1.2 mm Hg (0.2-2.3 mm Hg) and 4.1 cm/s (0.0-8.2 cm/s), respectively (both P < 0.05). CONCLUSIONS: Changing the positioning of stable patients with acute brain injury resulted in opposite changes of ICP versus brain oxygenation and circulation. This information supports the concept of an individualized approach to head positioning that is based on the multimodal monitoring of brain parameters.

Crossed anterior cerebral circulation in the anterior communicating artery complex, first case report with angiographic evidence.

INTRODUCTION: This case report illustrates a new variant in the anterior cerebral artery complex, identified during carotid angioplasty. CLINICAL CASE: A 50-year-old male patient diagnosed with left carotid stenosis was diagnosed and treated by a cerebral angiography. During the procedure, crossed circulation in the anterior cerebral artery was identified. The presence of this variation demanded to discard distal emboli or artery dissection. Angioplasty was performed and the patient followed up without neurological deficit. DISCUSSION: Among the most possible and prevalent variations in anterior circulation, none of them explain the phenomenon we observed. Therefore, a new variant is established. The knowledge about variants in cerebral circulation is important to rule out pathology. CONCLUSION: Cerebral diagnostic angiography has become more available and frequent because of the rising in endovascular tools to treat stroke patients. Considering this new variation and others is important to discard pathology.

Cerebrovascular carbon dioxide reactivity and flow-mediated dilation in young healthy South Asian and Caucasian European men.

South Asians living in the United Kingdom have a 1.5-fold greater risk of ischemic stroke than the general population. Impaired cerebrovascular carbon dioxide (CO2) reactivity is an independent predictor of ischemic stroke and cardiovascular mortality. We sought to test the hypothesis that cerebrovascular CO2 reactivity is reduced in South Asians. Middle cerebral artery blood velocity (MCA Vm) was measured at rest and during stepwise changes in end-tidal partial pressure of CO2 (PETCO2) in South Asian (n = 16) and Caucasian European (n = 18) men who were young (~20 yr), healthy, and living in the United Kingdom. Incremental hypercapnia was delivered via the open-circuit steady-state method, with stages of 4 and 7% CO2 (≈21% oxygen, nitrogen balanced). Cerebrovascular CO2 reactivity was calculated as the change in MCA Vm relative to the change in PETCO2. MCA Vm was not different in South Asians [59 (9) cm/s, mean (standard deviation)] and Caucasian Europeans [61 (12) cm/s; P > 0.05]. Similarly, cerebrovascular CO2 reactivity was not different between the groups [South Asian 2.53 (0.76) vs. Caucasian European 2.61 (0.81) cm·s-1·mmHg-1; P > 0.05]. Brachial artery flow-mediated dilation was lower in South Asians [5.48 (2.94)%] compared with Caucasian Europeans [7.41 (2.28)%; P < 0.05]; however, when corrected for shear rate no between-group differences in flow-mediated dilation were observed (P > 0.05). Flow-mediated dilation was not correlated with cerebrovascular CO2 reactivity measures. In summary, cerebrovascular CO2 reactivity and flow-mediated dilation corrected for shear rate are preserved in young healthy South Asian men living in the United Kingdom.NEW & NOTEWORTHY Previous reports have identified an increased risk of ischemic stroke and peripheral endothelial dysfunction in South Asians compared with Caucasian Europeans. The main finding of this study is that cerebrovascular carbon dioxide reactivity (an independent predictor of ischemic stroke) is not different in healthy young South Asian and Caucasian European men.