Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures

eLife, Journal Year: 2019, Volume and Issue: 8

Published: April 1, 2019

The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum parenchyma, a property defines the blood-brain blood-retina barriers. Exceptions to this pattern found in circumventricular organs (CVOs), small midline brain structures high permeability capillaries. In eye also present choriocapillaris, which supplies retinal pigment epithelium photoreceptors, ciliary body choroid plexus, sources aqueous humor cerebrospinal fluid, respectively. We show here (1) endothelial cells these vascular systems have very low beta-catenin signaling compared barrier-competent cells, (2) elevating leads partial conversion permeable barrier-type state. one CVO, area postrema, is maintained, part, local production Wnt inhibitory factor-1.

Language: Английский

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A Recurrent Neural Network model to predict blood–brain barrier permeability

Computational Biology and Chemistry, Journal Year: 2020, Volume and Issue: 89, P. 107377 - 107377

Published: Sept. 24, 2020

The rapid development of computational methods and the increasing volume chemical biological data have contributed to an immense growth in research. This field study is known as "chemoinformatics," which a discipline that uses machine-learning techniques extract, process, extrapolate from structures. One significant lines research chemoinformatics blood–brain barrier (BBB) permeability, aims identify drug penetration into central nervous system (CNS). In this research, we attempt solve problem BBB permeability by predicting compounds CNS. To accomplish goal: (i) First, overview provided chemoinformatics, its definition, applications, challenges, (ii) Second, broad view taken investigate previous deep-learning models permeability. Based on analysis models, three main challenges collectively affect classifier performance are identified, define "the triple constraints"; subsequently, map each constraint proposed solution, (iii) Finally, conclude endeavor proposing deep learning based Recurrent Neural Network model, predict (RNN-BBB model). Our model outperformed other studies literature scoring overall accuracy 96.53%, specificity score 98.08%. obtained results confirm addressing constraints substantially improves classification capability specifically when with low penetration.

Language: Английский

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Evaluation of Blood-Brain Barrier Integrity Using Vascular Permeability Markers: Evans Blue, Sodium Fluorescein, Albumin-Alexa Fluor Conjugates, and Horseradish Peroxidase

Methods in molecular biology, Journal Year: 2020, Volume and Issue: unknown, P. 87 - 103

Published: Jan. 1, 2020

Language: Английский

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Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1

Fluids and Barriers of the CNS, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 16, 2023

Abstract Regulation of the volume and electrolyte composition cerebrospinal fluid (CSF) is vital for brain development function. The Na-K-Cl co-transporter NKCC1 in choroid plexus (ChP) plays key roles regulating CSF by co-transporting ions mediating same-direction water movements. Our previous study showed ChP highly phosphorylated neonatal mice as K + level drastically decreases that overexpression accelerates clearance reduces ventricle size [1]. These data suggest mediates following birth mice. In this current study, we used CRISPR technology to create a conditional knockout mouse line evaluated Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction total embryonic intraventricular delivery Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied delayed perinatal . No gross morphological disruptions were observed cerebral cortex. extended our results showing rats shared characteristics with mice, including decreased expression level, increased phosphorylation state, levels compared adult. Collectively, these follow up support NKCC1’s role age-appropriate during development.

Language: Английский

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Mannose-binding lectin has a direct deleterious effect on ischemic brain microvascular endothelial cells

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2019, Volume and Issue: 40(8), P. 1608 - 1620

Published: Sept. 7, 2019

Mannose-binding lectin (MBL), an initiator of the pathway, is detrimental in ischemic stroke. MBL deposition on endothelium indicates beginning its actions, but downstream mechanisms are not clear yet. We investigated interactions with by exposing human brain microvascular endothelial cells (hBMECs) to protocols ischemia. Cells were exposed hypoxia or oxygen–glucose deprivation (OGD), and re-oxygenated serum (HS) recombinant (rhMBL). Hypoxic hBMECs HS showed increased complement system activation (C3c deposition, +59%) (+93%) than normoxic cells. Super-resolution microscopy internalization hypoxic altered cytoskeletal organization, indicating a potential action structure. To isolate effect, rhMBL after hypoxia/OGD. In both conditions, reduced viability (hypoxia: −25%, OGD: −34%) compared conditions without MBL, showing direct toxic effect. Ischemic also greater +143%, +126%) These results confirmed primary OGD (increased MBL-induced cell death: +226%, deposition: +104%). The present findings demonstrate that can exert deleterious effect vitro, independently from activation.

Language: Английский

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Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1862 - 1862

Published: Feb. 7, 2022

Caffeine, a common ingredient in energy drinks, crosses the blood-brain barrier easily, but kinetics of caffeine across blood-cerebrospinal fluid (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 no stimulant detected group) were examined. In addition, BCSFB model was constructed using human vascular endothelial cells choroid plexus epithelial separated by filter, effects 4-aminopyridine (4-AP), neuroexcitatory agent, studied. Caffeine concentrations right heart blood (Rs) cerebrospinal (CSF) compared cases: higher Rs than CSF A to B. model, 4-AP added upper layer, concentration lower layer measured. The suppressed, depending on concentration. Histomorphological examination suggested that involved inhibiting efflux CSF. Thus, simultaneous presence stimulants inhibits transfer BCSFB.

Language: Английский

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Neurofluids—Deep inspiration, cilia and preloading of the astrocytic network

Journal of Neuroscience Research, Journal Year: 2021, Volume and Issue: 99(11), P. 2804 - 2821

Published: July 29, 2021

Abstract With the advent of real‐time MRI, motion and passage cerebrospinal fluid can be visualized without gating exclusion low‐frequency waves. This imaging modality gives insights into low‐volume, rapidly oscillating cardiac‐driven movement as well sustained, high‐volume, slowly inspiration‐driven movement. Inspiration means a spontaneous or artificial increase in intrathoracic dimensions independent body position. Alterations thoracic diameter enable spinal epidural venous compartments to emptied filled, producing an upward surge inside spine during inspiration; this counterbalances downward pooling blood toward heart. Real‐time macroscale vivo observation method, could expand our knowledge neurofluid dynamics, including how astrocytic preloading is adjusted brain buoyancy turgor are maintained different postures zero gravity. Along with these findings, new microscale aquaporin‐mediated transfer, its sensing by cilia, tuning nitric oxide will reviewed. By incorporating clinical spanning several disciplines, certain disorders—congenital hydrocephalus Chiari malformation, idiopathic intracranial hypertension, adult hydrocephalus—are interpreted reviewed according current concepts, from basics interrelated systems their pathology.

Language: Английский

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Neurofluids – Deep Inspiration, Cilia and Preloading of the Astrocytic Network

Published: March 15, 2021

With the advent of real-time MRI, motion and passage cerebrospinal fluid can be visualized without gating exclusion low-frequency waves. This imaging modality gives insights into low-volume, rapidly oscillating cardiac-driven movement as well sustained, high-volume, slowly inspiration-driven movement.Inspiration means a spontaneous or artificial increase in intrathoracic dimensions independent body position. Alterations thoracic diameter enable spinal epidural venous compartments to emptied filled, producing an upward surge inside spine during inspiration; this counterbalances downward pooling blood toward heart.Real-time macroscale vivo observation method, could expand our knowledge neurofluid dynamics, including how astrocytic preloading is adjusted brain buoyancy turgor are maintained different postures zero gravity.Along with these findings, new microscale aquaporin-mediated transfer, its sensing by cilia tuning nitric oxide will reviewed. By incorporating clinical spanning several disciplines, certain disorders—congenital hydrocephalus Chiari malformation, idiopathic intracranial hypertension adult hydrocephalus—are interpreted reviewed according current concepts, from basics interrelated systems their pathology.

Language: Английский

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Edema-Swelling as a Standard Dose-Dependent Response of the Dentate Gyrus of the Hippocampal Formation to Acute Ischemia

Journal of Anatomy and Histopathology, Journal Year: 2021, Volume and Issue: 10(3), P. 15 - 26

Published: Sept. 20, 2021

The aim of research was to study structural changes and give a morphometric characteristic the edemaswelling manifestations dentate gyrus (DG) hippocampal formation in sexually mature white rats after common carotid artery occlusion (OCCA) different duration ligation (LCCA) arteries. Material methods. Acute ischemia simulated adult Wistar by 20-, 30-, 40-min Histological (staining with hematoxylin-eosin, according Nissl), immunohistochemical (NSE, MAP-2, GFAP) techniques were used for morphological investigations. Morphometric analysis edema-swelling carried out on samples stained hematoxylin-eosin using plugins ImageJ 1.53 program (Find Maxima, Find Foci). Statistical hypotheses (nonparametric tests) tested Statistica 8.0 software. Results. After reperfusion, pronounced involution large zones occurred DG groups I, II, III 7–14 days, group IV (ligation) persisted 30 days. Similar dynamics recorded molecular polymorphic layer DG, but values integral variable chosen assess (the total intensity peak pixels) different. largest relative area brightest peaks detected bilateral ОССА (groups II III) LCCA (group IV), smallest – unilateral I). It is significant that mild (20- 30-min ОССА), parameter increased only 1 3 then decreased. more severe (40-min similar overhydration observed 1–7 With LССА, high level noted throughout observation period, as evidenced all peaks. Statistically differences found when comparing periods, between 14 periods (ANOVA Kruskal–Wallis test; Mann–Whitney U-test). Conclusion. LССА restoration structures sensory input hippocampus occurs together long-term preservation signs hyperhydration neuropil, perineuronal perivascular spaces (legs astrocytes). extreme degree these evidences disruption drainage-detoxification function astrocytes. In ОССА, recommended be considered condition implementation mechanisms sanogenesis nervous tissue.

Language: Английский

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Relation between the Severity of the Sensorimotor Cortical Edema with Cell Swelling and the Duration of Common Carotid Artery Occlusion in Rats (Morphometric Study)

General Reanimatology, Journal Year: 2021, Volume and Issue: 17(5), P. 111 - 128

Published: Oct. 23, 2021

The aim of the study . To examine changes in structure and morphometry sensorimotor cortical edema with cell swelling mature white rats after common carotid artery occlusion various durations. Material methods Acute ischemia was modeled on adult Wistar by 20-, 30- 40-min arteries (CCA). Histological (hematoxylin-eosin Nissl staining), immunohistochemical (NSE, MAP-2, GFAP) morphometric were used. Morphometry assessed hematoxylin eosin-stained specimens using ImageJ 1.53 plug-ins (Find Maxima, Find Foci). Statistical hypothesis testing (nonparametric criteria) performed Statistica 8.0 software. Results In cortex (SMC) 20, 30 40 minutes CCA signs cytotoxic brain appeared, focal destructive adaptive neurons astroglia evolved. persisted throughout observation period (7 days). increase relative area, number zones their hydration (pixel brightness) significant. On days 1 3 occlusion, some SMC astrocyte processes underwent destruction. Subpial perivascular suffered to a greater extent. Mild moderate (after unilateral 30-min occlusion) severe bilateral scattered structural functional large areas clearing «porous» neuropil, perineuronal developed. latter associated reduction total neuronal density. Conclusion After CCA, cellular appeared amid dystrophic necrotic pyramidal activated neuroglial cells. extent, evident three CCA.

Language: Английский

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