Brain Vascular System Research Articles

Amyloid Beta-Mediated Neurovascular Toxicity in Alzheimer's Disease.

The brain vascular system receives one-fifth of the total oxygen from the cardiac output, and this transport system is highly dependent on blood-brain barrier (BBB) integrity. The cerebral blood flow is controlled by neurovascular coupling through neurovascular units (NVUs). The NVU includes different types of cells, such as mural cells, astrocytes, pericytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). The cellular composition of NVU varies throughout the vascular tree. Amyloid β (Aβ) is abundantly present in the central nervous system, but the pathological accumulation of misfolded Aβ protein causes vascular damage, resulting in neurovascular dysfunction. Aβ aggregation can activate the astrocytes and endothelial cells. It is followed by pericyte degeneration which results in dysregulation of cerebral blood flow (CBF), neurovascular uncoupling, and BBB breakdown. Thus, understanding the cellular and molecular mechanisms of Aβ-induced neurovascular toxicity is crucial for determining normal and diseased brain function. This chapter discusses the components of NVU, neurovascular uncoupling, Aβ-induced cerebrovascular reactivity, and cerebral blood flow reduction in neurodegenerative disorders, with special emphasis on Alzheimer's disease.

Prenatal diagnosis and characterization of extra-axial, supratentorial pial arteriovenous malformation using high-resolution transvaginal neurosonography.

Prenatal diagnosis and characterization of extra-axial, supratentorial pial arteriovenous malformation using high-resolution transvaginal neurosonography.

Expert consensus on management strategy of non-traditional vascular health risk factors in China(2022 the first report)

Vascular related diseases of the heart, brain and peripheral vascular system are main injury for human health. To change this situation, we need to change the previous diagnosis and treatment mode. Non-traditional risk factors may affect vascular health. We do not have uniform standard for evaluation and management of non-traditional vascular health risk factors. We should not only focus on the traditional risk factors, but also consider the impact of the risk factors on vascular health which have not received enough attention nor identified in the past, such as Beijing vascular health stratification (BVHS), sleep disturbance, dental diseases, mental stress, erectile dysfunction and inappropriate exercise. This consensus will provide suggestions for the examination, evaluation and management of non-traditional vascular health risk factors, provide references for doctors to make decisions, and standardize non-traditional risk factors and diagnosis and treatment. Further attention to non-traditional vascular health risk factors will provide new ideas and broaden new horizons for the prevention and control of vascular related diseases and the lifelong maintenance of vascular health.

Reduced white matter microstructural integrity in prediabetes: Is early glucose dysmetabolism the culprit?

Diabetes is a key risk factor for various aging-related brain diseases such as stroke1 and Alzheimer's disease.2 Through multiple pathways, diabetes can compromise the brain vascular system and cause widespread brain damage,3 including brain atrophy, white matter hyperintensities, lacunar infarcts,4 etc. Since early detection and management of diabetes may be beneficial for delaying the progression of related diseases, much attention has recently been given to prediabetes. Prediabetes is a health condition defined by glycemic variables above normal levels but below the diabetes thresholds.

Detecting Three-Dimensional Vascular Networks in the Mouse Embryonic Hindbrain.

Blood vessel formation is a fine-regulated process and interfering with blood vessel formation causes embryonic lethality as well as associated with many diseases in the adult, including inflammatory, ischemic, and cancer metastatic diseases. Brain contains abundant blood vessels and has some unique physiological functions, such as blood-brain barrier. Due to the thickness and opaque characters of the tissues, it is a challenge to visualize the three-dimensional structures of the brain blood vessels in the mouse. Therefore, establishing a protocol to display the three-dimensional structures in the brain is required for exploring the regulatory molecular mechanisms in brain blood vessel formation. In this manuscript, we introduced a whole-mount and a vibratome thick section of mouse embryonic hindbrain to display the three-dimensional structures of brain vascular system.

Chapter 4 - Brain vascular biology

The complex development of the brain vascular system can be broken down by embryonic stages and anatomic locations, which are tightly regulated by different factors and pathways in time and spatially. The adult brain is relatively quiescent in angiogenesis. However, under disease conditions, such as trauma, stroke, or tumor, angiogenesis can be activated in the adult brain. Disruption of any of the factors or pathways may lead to malformed vessel development. In this chapter, we will discuss factors and pathways involved in normal brain vasculogenesis and vascular maturation, and the pathogenesis of several brain vascular malformations.

Mapping endothelial-cell diversity in cerebral cavernous malformations at single-cell resolution.

Cerebral cavernous malformation (CCM) is a rare neurovascular disease that is characterized by enlarged and irregular blood vessels that often lead to cerebral hemorrhage. Loss-of-function mutations to any of three genes results in CCM lesion formation; namely, KRIT1, CCM2, and PDCD10 (CCM3). Here, we report for the first time in-depth single-cell RNA sequencing, combined with spatial transcriptomics and immunohistochemistry, to comprehensively characterize subclasses of brain endothelial cells (ECs) under both normal conditions and after deletion of Pdcd10 (Ccm3) in a mouse model of CCM. Integrated single-cell analysis identifies arterial ECs as refractory to CCM transformation. Conversely, a subset of angiogenic venous capillary ECs and respective resident endothelial progenitors appear to be at the origin of CCM lesions. These data are relevant for the understanding of the plasticity of the brain vascular system and provide novel insights into the molecular basis of CCM disease at the single cell level.

Aerobic exercise increases sprouting angiogenesis in the male rat motor cortex.

Exercise is beneficial to brain health, and historically, the advantageous effects of exercise on the brain have been attributed to neuronal plasticity. However, it has also become clear that the brain vascular system also exhibits plasticity in response to exercise. This plasticity occurs in areas involved in movement, such as the motor cortex. This experiment aimed to further characterize the effects of exercise on structural vascular plasticity in the male rat motor cortex, by specifically identifying whether features of angiogenesis, the growth of new capillaries, or changes in vessel diameter were present. Male rats in the exercise group engaged in a 5-week bout of voluntary wheel running, while a second group of rats remained sedentary. After the exercise regimen, vascular corrosion casts, resin replicas of the brain vasculature, were made for all animals and imaged using a scanning electron microscope. Results indicate sprouting angiogenesis was the primary form of structural vascular plasticity detected in the motor cortex under these aerobic exercise parameters. Additionally, exercised rats displayed a slight increase in capillary diameter and expanded endothelial cell nuclei diameters in this region.

The Possibilities of Single-Pill Combinations of Antihypertensive Drugs in Cerebroprotection: Focus on the Combination of Amlodipine with Ramipril

Stroke remains one of the leading causes of death and disability both worldwide and in Russia. Acute cerebrovascular events have many risk factors, among them the most important is arterial hypertension (AH), which predisposes to the stroke development through the direct effect of increased hydrostatic blood pressure on the brain vascular system, followed by arterial remodeling and an increase in their stiffness. In addition, excessive blood pressure variability, activation of the tissue renin-angiotensin-aldosterone system, as well as target-organ damage - primarily the heart in the form of left ventricular hypertrophy, kidneys in the form of microalbuminuria and decrease in glomerular filtration rates. An additional risk factor for stroke is hyperuricemia, which is included in the current European and Russian guidelines for the management of AH as one of the new risk factors in patients with this disease. The state-of-the-art approach to antihypertensive therapy is the using of antihypertensive single-pill combinations, one of the frontline combinations in the absence of special clinical conditions is a combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker. The reference drugs in both classes due to large body of evidence are ramipril and amlodipine, respectively. These drugs provide a high level of brain protection, not only due to the ultra-long and powerful antihypertensive action, but also through a unique potential in target-organ protection via left ventricular hypertrophy regression, antiatherosclerotic effects and improved endothelial function, renal protection, as well as the ability to decrease uric acid in the blood.

The endocast of the late Middle Paleolithic Manot 1 specimen, Western Galilee, Israel

Studying endocasts has long allowed anthropologists to examine changes in the external topography and the overall size of the brain throughout the evolutionary history of hominins. The nearly complete calvaria of Manot 1 presents an opportunity to gain insights into the external brain morphology, vascular system, and dimensions of the brain of this late Middle Paleolithic hominin. Detailed size and shape analyses of the Manot 1 endocast indicate a modern Homo sapiens anatomy, despite the presence of some primitive features of the calvaria. Traits considered to be derived endocranial features for H. sapiens are present in Manot 1, including an elongated parietal sagittal chord with an elevated superior part of the hemisphere, a widened posterior part of the frontal lobes, a considerable development of the parietal reliefs such as the supramarginal lobules, and a slight posterior projection of the occipital lobes. These findings, together with data presented in previous studies, rule out the possibility of a direct Neanderthal ancestry for the Manot 1 hominin and instead confirm its affiliation with H. sapiens. The Manot 1 calvaria is more similar to that of later Upper Paleolithic H. sapiens than it is to the earlier Levantine populations of Skhul and Qafzeh. The late Middle Paleolithic date of Manot 1 provides an opportunity to analyze the recent developments in human cerebral morphology and organization.

Мальформации как нарушение фрактальной структуры кровеносной системы организма

The article contains a description of mathematical models, the bases of which is the representation of the body circulatory system as a multifractal object. As examples, we consider the solution of two problems. The first issue is related to the normal state of the body’s life support system, namely, heat transfer in human skin. The model base is the equations of hydrodynamics and heat transfer. Quantitative results of calculating heat fluxes in three layers of the dermis are presented. The second issue deals with a violation of fractality due to the presence of arteriovenous malformation in the brain vascular system. The SolidWorks 2017 Flow Simulation software product serves as the basis for the implementation of a blood flow model in the presence of malformation. As a result of the simulation, data on the velocities and blood flow in the vessels were obtained for various cases of malformations.

Planning Method for Safety Neurosurgical and Computed Tomography Contrast-Data Set Visualization

Discussed the issues' associated with the development of a computed neurosurgery planning system. An important part is to determine the value of invasive surgical access. The study purpose is to design a methodology for finding the shortest distance between surgical target and peripheral point of the brain tissue with strict adherence considering the type of the brain anatomical structure existing in the path of surgical track (risk map), these two condition used in companion to determine the risk value of the surgical access. The study method consists of two algorithms for calculating the shortest surgical access to the target and assuring the safety by avoiding high-density tissues identification method “internal map” describing the anatomy of the brain such as bones. An algorithm for automatic identification of brain vascular system also was designed. The structural diagram of the contrast data visualization system, using computed tomography data, was thoroughly discussed. Also, trying to contribute in solving issues facing developers of modern medical imaging visualization systems to select the most appropriate method from the whole arsenal of algorithms and processing models concerning displaying brain surgical zone using image registration and optical tracking system. The visualization of the target zone is carried out according to an internal reference landmark points inside the center of the brain as well as an automatic algorithm for contour recognition was applied. Moreover, the optical tracking system was used to assess the navigation accuracy of determining the position of the surgical instrument outside the patient head. Algorithms necessary for operational planning also was included, and the proposed method was applied in a pilot study with simulation mode to human brain model, in order to target a specific surgical zone, and as a result, the system suggested (24) possible surgical track, among them, were selected the best and safest access. The total error of a surgical instrument targeting was less than 3 mm (in average 2.6 mm).

In Vitro Modulation of Redox and Metabolism Interplay at the Brain Vascular Endothelium: Genomic and Proteomic Profiles of Sulforaphane Activity

Sulforaphane (SFN) has been shown to protect the brain vascular system and effectively reduce ischemic injuries and cognitive deficits. Given the robust cerebrovascular protection afforded by SFN, the objective of this study was to profile these effects in vitro using primary mouse brain microvascular endothelial cells and focusing on cellular redox, metabolism and detoxification functions. We used a mouse MitoChip array developed and validated at the FDA National Center for Toxicological Research (NCTR) to profile a host of genes encoded by nuclear and mt-DNA following SFN treatment (0–5 µM). Corresponding protein expression levels were assessed (ad hoc) by qRT-PCR, immunoblots and immunocytochemistry (ICC). Gene ontology clustering revealed that SFN treatment (24 h) significantly up-regulated ~50 key genes (>1.5 fold, adjusted p < 0.0001) and repressed 20 genes (<0.7 fold, adjusted p < 0.0001) belonging to oxidative stress, phase 1 & 2 drug metabolism enzymes (glutathione system), iron transporters, glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid metabolism and mitochondrial biogenesis. Our results show that SFN stimulated the production of ATP by promoting the expression and activity of glucose transporter-1, and glycolysis. In addition, SFN upregulated anti-oxidative stress responses, redox signaling and phase 2 drug metabolism/detoxification functions, thus elucidating further the previously observed neurovascular protective effects of this compound.

Serum Ferritin and Plasma Fibrinogen Level in Acute Ischemic Stroke

Acute ischemic stroke is the primary pathology of brain vascular system that temporarily or permanently affects brain functions as a result of ischemia. In ischemic stroke events, many biochemical and immunological reactions occur secondarily in response to the reduced cerebral blood flow. Brain tissue damage after acute ischemic stroke is mediated partly by inflammation induced by ischemia-reperfusion injury. It is thought that acute ischemic stroke due to cerebral ischemia triggers acute phase reaction and the blood concentration of ferritin and fibrinogen could rise during brain infarction. This study was carried out in the Department of Biochemistry, Sylhet MAG Osmani Medical College during the period of July 2015 to June 2016 to evaluate the status of ferritin and fibrinogen in acute ischemic stroke patients. For this study serum ferritin and plasma fibrinogen level were assessed in 50 acute ischemic stroke patients and 50 normal individuals. Data were analyzed with the help of SPSS version 19.0. Unpaired Student's 't' test and Mann-Whitney U test were done to see the level of significance. Findings of the study revealed that serum ferritin and plasma fibrinogen levels were 83.1 ng/ml and 190.6 mg/dl in subjects with acute ischemic stroke, while in control subjects these were 41.3 ng/ml and 177.0 mg/dl respectively. Study showed that serum ferritin and plasma fibrinogen levels were significantly higher in patients with ischemic acute stroke compared to that of normal controls (p&lt;0.001). It may be concluded that serum ferritin and plasma fibrinogen levels are significantly increased in acute ischemic stroke.Bangladesh J Med Biochem 2017; 10(1): 16-20

PLATELET AGGREGATION IN ACUTE CORONARY SYNDROME

Haemostatic system is the mechanism that controls response of bleeding or thrombosis, so that thrombogenesis and fibrinolysis are inbalance. Obstruction of brain and heart vascular system often occurred, because of the hyperactivity of thromboses function that causesthrombosis. CBC, blood glucose, lipid profile and cardiac enzyme assay were performed on acute coronary syndrome patients at theEmergency Department as well as at the normal control. In this study, each group consist of 10 patients. Platelet aggregation test wasmeasured with turbidimetric method using Helena Agram aggregometer. ADP and epinephrine 5 and 10 µM were used as the agonists.There was significant difference in the mean total cholesterol, LDL and blood sugar level in the acute coronary syndrome patients thanthe control group. Platelet aggregations with ADP 1 and 5 µM were significantly different in the acute coronary syndrome patients thanthe control one. In this study were found patients aged above 50 years old have platelet aggregation with ADP 10 µM, which differsignificantly than the control group.

Chapter 2 - The cerebrospinal fluid and barriers – anatomic and physiologic considerations

The cerebrospinal fluid (CSF) space consists of the intracerebral ventricles, subarachnoid spaces of the spine and brain (e.g., cisterns and sulci), and the central spinal cord canal. The CSF protects the central nervous system (CNS) in different ways involving metabolic homeostasis, supply of nutrients, functioning as lymphatic system, and regulation of intracranial pressure. CSF is produced by the choroid plexus, brain interstitium, and meninges, and it circulates in a craniocaudal direction from ventricles to spinal subarachnoid space from where it is removed via craniocaudal lymphatic routes and the venous system. The CSF is renewed 3-5 times daily and its molecular constituents are mainly blood-derived (80%), while the remainder consists of brain-derived and intrathecally produced molecules (20%). The CSF space is separated from the vascular system by the blood-CSF barrier (BCB), whereas the blood-brain barrier (BBB), responsible for maintaining the homeostasis of the brain, is located between brain parenchyma and vascular system. Although both barriers have similar functions, they differ with regard to their morphologic and functional properties. Both barrier systems are permeable not only for small molecules, but also for macromolecules and circulating cells. The transport of molecules across the BBB and BCB is regulated by passive diffusion (e.g., albumin, immunoglobulins) and facilitated or active transport (e.g., glucose). The extracellular space volume, potassium buffering, CSF circulation, and interstitial fluid absorption are mainly regulated by aquaporin-4 channels, which are abundantly located at the blood-brain and brain-CSF interfaces. The composition of CSF shows a high dynamic range, and the levels of distinct proteins vary due to several influencing factors, such as site of production (brain or blood-derived), site of sampling (ventricular or lumbar), CSF flow rate (BCB function), diurnal fluctuations of CSF production rate, and finally, molecular size of blood-derived proteins (IgM vs. albumin) and circadian rhythm (glucose, prostaglandin D synthase). Alterations of lumbar CSF are mainly influenced by processes of the CNS located adjacent to the ventricular and spinal CSF space and less by pathologies in cortical areas remote from the ventricles.

Cerebral vasoreactivity: Concordance of breath holding test and acetazolamide injection in current practice: 20 cases of asymptomatic carotid artery stenosis

Cerebral vasoreactivity (CVR) is the ability of the brain's vascular system to keep cerebral blood inflow stable. Impaired CVR is a risk marker of stroke in patients with asymptomatic carotid stenosis. The gold standard to assess CVR with transcranial ultrasound is acetazolamide (ACTZ) injection. The breath holding test (BHT) might be easier to perform. CVR proved to be efficient in laboratory conditions but not in routine practice. To study the validity of BHT versus ACTZ in routine practice in a vascular exploration unit in patients with asymptomatic carotid stenosis. Study of concordance of BHT and ACTZ, to assess CVR in patients consecutively explored on the same day. Eighteen patients with 20 carotid stenosis were included. The temporal window was missing in 20% of cases. Only 11 out of the 20 procedures were analyzed. Concordance was low between BHT and ACTZ to assess CVR (k=0.3714). BHT cannot replace ACTZ injection. It might be a first-step test so that ACTZ injection might be avoided if CVR is normal. Our present results must be confirmed by further study enrolling many more patients.

Oxidative stress affects processing of amyloid precursor protein in vascular endothelial cells.

BackgroundOxidative stress is thought to be a key player in the pathogenesis of neurodegenerative dementia, including Alzheimer’s disease (AD). It has been assumed that oxidative stress contributes to the ß-amyloid deposition in cerebral blood vessels.MethodsIn order to prove this hypothesis, we examined the effect of oxidative stress on the processing of amyloid precursor protein (APP) in primary endothelial cells (EC) derived from cerebral cortical tissue of transgenic Tg2576 mice. Following exposure of EC by 1 μM hydrogen peroxide for up to 48 hours, formation and secretion of APP cleavage products sAPPα and sAPPß into the culture medium as well as the expression of endothelial APP were assessed.ResultsOxidative stress resulted in enhanced secretion of sAPPß into the culture medium as compared to controls (absence of hydrogen peroxide), which was accompanied by an increased APP expression, induction of VEGF synthesis, nitric oxide and oxygen free radicals productions, and differential changes of endothelial phospo-p42/44 MAPK expression.ConclusionThe data suggest that oxidative stress may represent a major risk factor in causing Aß deposition in the brain vascular system by initiating the amyloidogenic route of endothelial APP processing. The enhanced β-secretase activity following oxidative stress exposure, possibly promoted by phosphorylation of p42/44 MAPK.

Review: Roles for astrocytes in epilepsy: insights from malformations of cortical development.

Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood-brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro-inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence.

Correction of autonomic nervous system indicators due to the effect of geomagnetic perturbations in patients with remote after effects of closed traumatic brain injury

Ко rshnyak V. А ., G о zh е nk о А. I ., N а sibullin B. А . Correction of autonomic nervous system indicators due to the effect of geomagnetic perturbations in patients with remote after effects of closed traumatic brain injury. Journal of Education, Health and Sport. 2016;6(8):296-304. eISSN 2391-8306. DOI http://dx.doi.org/10.6084/m9.figshare.3749121 http://ojs.ukw.edu.pl/index.php/johs/article/view/3760 https://pbn.nauka.gov.pl/sedno-webapp/works/743659 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.08.2016. Revised 08.08.2016. Accepted: 19.08.2016. CORRECTION OF AUTONOMIC NERVOUS SYSTEM INDICATORS DUE TO THE EFFECT OF GEOMAGNETIC PERTURBATIONS IN PATIENTS WITH REMOTE AFTER EFFECTS OF CLOSED TRAUMATIC BRAIN INJURY V. А . Ко rshnyak 1 , А. I . G о zh е nk о 2 , B. А . N а sibullin 3 1 State Institution Institute of neurology, psychiatry and narcology of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine 2 Ukrainian Scientific and Research of Transport Medicine of the Ministry of Health of Ukraine, Odessa, Ukraine 3 T he Ukrainian s cientific and r esearch i nstitute of m edical r ehabilitation and b alneology of the Ministry of h ealth of Ukraine , Odessa, Ukraine . Abstract The authors show that in modern biology, life is seen as the ability of living matter, and namely in medicine – the ability of human body, to maintain the existence in natural environment. From this perspective, it is extremely necessary to synchronize the activity of body structures among themselves taking into account the changes of environmental factors. Achieving the harmony between the body activity and environmental changes is carried out using an external pacemaker of life processes’ activity, the role of which is performed by the geomagnetic field (GMF). This became possible due to the fact that the life processes are cyclical, i.e. they possess rhythmic characteristics, and GMF is an electromagnetic field which is changing its characteristics rhythmically. The material for the present study were the data obtained during the neurological examination of 20 healthy people and 100 patients with remote consequences of CTBI which were treated in the clinic of autonomic nervous system pathology of the SI Institute of neurology, psychiatry and narcology of the NAMS of Ukraine. The results investigations have showed that geomagnetic perturbations, which modify the GMF parameters, exacerbate the disorders of VNS in patients with remote after effects of CTBI. It is associated with the increased desynchronization of the activity of suprasegmental structures of VNS and with breach of brain vascular system’s status that occurs during a magnetic storm. The acupuncture that is aimed at restoring of synchronization of activity of suprasegmental structures of VNS significantly reduces its sensitivity to the geomagnetic disturbances. Keywords: magnetic storm, closed head injury, autonomic nervous system.