scholarly journals Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results

2020 ◽  
Vol 234 (11) ◽  
pp. 1223-1234 ◽  
Author(s):  
John C Vardakis ◽  
Dean Chou ◽  
Liwei Guo ◽  
Yiannis Ventikos
Keyword(s):  
Large Scale ◽  
Fluid Transport ◽  
Neurovascular Unit ◽  
Cerebrovascular Diseases ◽  
Glymphatic System ◽  
The Central Nervous System ◽  
Multiple Network ◽  
High Throughput Imaging ◽  
Poroelastic Theory ◽  
Variability Model

The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.

scholarly journals In Vivo Targeting of the Neurovascular Unit: Challenges and Advancements

2021 ◽  
Author(s):  
Oandy Naranjo ◽  
Olivia Osborne ◽  
Silvia Torices ◽  
Michal Toborek
Keyword(s):  
Multiple Sclerosis ◽  
Fluid Transport ◽  
Neurological Diseases ◽  
Neurovascular Unit ◽  
Protein Markers ◽  
Transport Studies ◽  
Selective Targeting ◽  
The Central Nervous System ◽  
Made In

AbstractThe blood–brain barrier (BBB) is essential for the homeostasis of the central nervous system (CNS). Functions of the BBB are performed by the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, basement membrane, and neurons. NVU cells interact closely and together are responsible for neurovascular coupling, BBB integrity, and transendothelial fluid transport. Studies have shown that NVU dysfunction is implicated in several acute and chronic neurological diseases, including Alzheimer’s disease, multiple sclerosis, and stroke. The mechanisms of NVU disruption remain poorly understood, partially due to difficulties in selective targeting of NVU cells. In this review, we discuss the relative merits of available protein markers and drivers of the NVU along with recent advancements that have been made in the field to increase efficiency and specificity of NVU research.

scholarly journals The Glymphatic System (En)during Inflammation

2021 ◽  
Vol 22 (14) ◽  
pp. 7491
Author(s):  
Frida Lind-Holm Mogensen ◽  
Christine Delle ◽  
Maiken Nedergaard
Keyword(s):  
Fluid Transport ◽  
Neurological Diseases ◽  
Lymphatic Vessels ◽  
Perivascular Spaces ◽  
Fluid Exchange ◽  
Glymphatic System ◽  
The Central Nervous System ◽  
The Brain ◽  
Privileged Site ◽  
Vascular Compartment

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.

Assessment of quality of life in patients with the effects of transient ischemic stroke

2016 ◽  
pp. 37-39
Author(s):  
A. Babirad
Keyword(s):  
Quality Of Life ◽  
Ischemic Stroke ◽  
Large Scale ◽  
Cerebrovascular Diseases ◽  
Control Measures ◽  
Sociological Research ◽  
Cerebrovascular Events ◽  
Sf 36 ◽  
Angioplasty And Stenting

Cerebrovascular diseases are a problem of the world today, and according to the forecast, the problem of the near future arises. The main risk factors for the development of ischemic disorders of the cerebral circulation include oblique and aging, arterial hypertension, smoking, diabetes mellitus and heart disease. An effective strategy for the prevention of cerebrovascular events is based on the implementation of large-scale risk control measures, including the use of antiagregant and anticoagulant therapy, invasive interventions such as atheromectomy, angioplasty and stenting. In this connection, the efforts of neurologists, cardiologists, angiosurgery, endocrinologists and other specialists are the basis for achieving an acceptable clinical outcome. A review of the SF-36 method for assessing the quality of life in patients with the effects of transient ischemic stroke is presented. The assessment of quality of life is recognized in world medical practice and research, an indicator that is also used to assess the quality of the health system and in general sociological research.

Brain stem – from general view to computational model based on switchboard rules of operation

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Włodzisław Duch ◽  
Dariusz Mikołajewski
Keyword(s):  
Brain Stem ◽  
Large Scale ◽  
Ionic Channels ◽  
General View ◽  
The Central Nervous System ◽  
Network States ◽  
Large Scale Simulations ◽  
Influence Of Noise ◽  
The Brain ◽  
Sufficient Precision

Abstract Despite great progress in understanding the functions and structures of the central nervous system (CNS) the brain stem remains one of the least understood systems. We know that the brain stem acts as a decision station preparing the organism to act in a specific way, but such functions are rather difficult to model with sufficient precision to replicate experimental data due to the scarcity of data and complexity of large-scale simulations of brain stem structures. The approach proposed in this article retains some ideas of previous models, and provides more precise computational realization that enables qualitative interpretation of the functions played by different network states. Simulations are aimed primarily at the investigation of general switching mechanisms which may be executed in brain stem neural networks, as far as studying how the aforementioned mechanisms depend on basic neural network features: basic ionic channels, accommodation, and the influence of noise.

scholarly journals Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system

2020 ◽  
Vol 40 (10) ◽  
pp. 1975-1986
Author(s):  
Nicholas B Bèchet ◽  
Tekla M Kylkilahti ◽  
Bengt Mattsson ◽  
Martina Petrasova ◽  
Nagesh C Shanbhag ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Fluid Transport ◽  
Light Sheet ◽  
Brain Parenchyma ◽  
Sleep State ◽  
Glymphatic System ◽  
Light Sheet Microscopy ◽  
Highly Active ◽  
Quantitative Analyses ◽  
Light Sheet Fluorescence Microscopy

Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.

scholarly journals Astroglial Integrins in the Development and Regulation of Neurovascular Units

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hironobu Tanigami ◽  
Takayuki Okamoto ◽  
Yuichi Yasue ◽  
Motomu Shimaoka
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Energy Demand ◽  
Vascular Tone ◽  
Neurovascular Unit ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
The Brain ◽  
Signaling Activity ◽  
Cerebral Vascular

In the neurovascular units of the central nervous system, astrocytes form extensive networks that physically and functionally connect the neuronal synapses and the cerebral vascular vessels. This astrocytic network is thought to be critically important for coupling neuronal signaling activity and energy demand with cerebral vascular tone and blood flow. To establish and maintain this elaborate network, astrocytes must precisely calibrate their perisynaptic and perivascular processes in order to sense and regulate neuronal and vascular activities, respectively. Integrins, a prominent family of cell-adhesion molecules that support astrocytic migration in the brain during developmental and normal adult stages, have been implicated in regulating the integrity of the blood brain barrier and the tripartite synapse to facilitate the formation of a functionally integrated neurovascular unit. This paper describes the significant roles that integrins and connexins play not only in regulating astrocyte migration during the developmental and adult stages of the neurovascular unit, but also in general health and in such diseases as hepatic encephalopathy.

Experimental modeling and clinical technology of photodynamic therapy

2020 ◽  
pp. 72-80
Author(s):  
Daria Aleksandrovna Krapivnitskaya ◽  
Kseniya Vyacheslavovna Kuznetsova ◽  
Igor Valentinovich Barskov ◽  
Vladimir Germanovich Taktarov ◽  
Vladimir Yurievich Pereverzev
Keyword(s):  
Central Nervous System ◽  
Photodynamic Therapy ◽  
Large Scale ◽  
Clinical Medicine ◽  
Practical Importance ◽  
Skin Lesions ◽  
Clinical Aspects ◽  
Regenerative Processes ◽  
Ischemic Tissue ◽  
The Central Nervous System

In recent years, the amount of large-scale experimental and clinical studies has increased considerably leading to the development of techniques and their widespread use both in their field and serving as a basis for the combination of even paradoxically incompatible areas of experimental and clinical medicine. The authors consider one of the main objectives of this work to identify a stable correlation between experimental pathomorphological study in ischemic tissue lesion and a therapeutic effect in dermatology in various pathological processes since the fundamental method in both cases is represented by a photochemical effect on the central nervous system and skin. These studies are not only of theoretical value but also of great practical importance both for neurological (search for medicines used to stimulate regenerative processes in ischemic pathology) and dermatological clinical aspects (ablation method of photodynamic therapy for various skin lesions).

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases

2018 ◽  
Vol 20 (1) ◽  
pp. 78 ◽  
Author(s):  
Huiju Lee ◽  
Yoon Choi
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Neurovascular Unit ◽  
Vascular Diseases ◽  
Cell Types ◽  
Cns Injury ◽  
Perivascular Cells ◽  
Major Barrier ◽  
The Central Nervous System

Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders. CNS injury elicits responses from activated glia (e.g., astrocytes, oligodendrocytes, and microglia) and from damaged perivascular cells (e.g., pericytes and endothelial cells). Most brain lesions cause extensive proliferation and growth of existing glial cells around the site of injury, leading to reactions causing glial scarring, which may act as a major barrier to neuronal regrowth in the CNS. In addition, damaged perivascular cells lead to the breakdown of the blood-neural barrier, and an increase in immune activation, activated glia, and neuroinflammation. The present review discusses the regenerative role of HO metabolites, such as CO and BR, in various vascular diseases of the CNS such as stroke, traumatic brain injury, diabetic retinopathy, and Alzheimer’s disease, and the role of several other signaling molecules.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

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