scholarly journals Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in the Drainage of Fluids and Solutes

2021 ◽  
Vol 11 ◽  
Author(s):  
Nivedita Agarwal ◽  
Roxana Octavia Carare
Keyword(s):  
Cerebral Arteries ◽  
Lymphatic Vessels ◽  
Vascular Anatomy ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Basement Membranes ◽  
Cervical Lymph Nodes ◽  
Waste Products ◽  
Venous Sinuses ◽  
The Brain

The cerebral vasculature is made up of highly specialized structures that assure constant brain perfusion necessary to meet the very high demand for oxygen and glucose by neurons and glial cells. A dense, redundant network of arteries is spread over the entire pial surface from which penetrating arteries dive into the cortex to reach the neurovascular units. Besides providing blood to the brain parenchyma, cerebral arteries are key in the drainage of interstitial fluid (ISF) and solutes such as amyloid-beta. This occurs along the basement membranes surrounding vascular smooth muscle cells, toward leptomeningeal arteries and deep cervical lymph nodes. The dense microvasculature is made up of fine capillaries. Capillary walls contain pericytes that have contractile properties and are lined by a highly specialized blood–brain barrier that regulates the entry of solutes and ions and maintains the integrity of the composition of ISF. They are also important for the production of ISF. Capillaries drain into venules that course centrifugally toward the cortex to reach cortical veins and empty into dural venous sinuses. The walls of the venous sinuses are also home to meningeal lymphatic vessels that support the drainage of cerebrospinal fluid, although such pathways are still poorly understood. Damage to macro- and microvasculature will compromise cerebral perfusion, hamper the highly synchronized movement of neurofluids, and affect the drainage of waste products leading to neuronal and glial degeneration. This review will present vascular anatomy, their role in fluid dynamics, and a summary of how their dysfunction can lead to neurodegeneration.

The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain

2017 ◽  
Vol 131 (22) ◽  
pp. 2745-2752 ◽  
Author(s):  
Howard Dobson ◽  
Matthew MacGregor Sharp ◽  
Richard Cumpsty ◽  
Theodore P. Criswell ◽  
Tyler Wellman ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Basement Membranes ◽  
Post Mortem ◽  
Cervical Lymph Nodes ◽  
The Brain

Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.

Neural glymphatic system: Clinical implications and potential importance of melatonin

2021 ◽  
Vol 4 (4) ◽  
pp. 551-565
Author(s):  
Ryan D Bitar ◽  
Jorge L Torres-Garza ◽  
Russel J Reiter ◽  
William T Phillips
Keyword(s):  
Lymph Nodes ◽  
Subarachnoid Space ◽  
Slow Wave Sleep ◽  
Lymphatic Vessels ◽  
Amyloid Β ◽  
Secretory Product ◽  
Cervical Lymph Nodes ◽  
Waste Products ◽  
Glymphatic System ◽  
The Brain

The central nervous system was thought to lack a lymphatic drainage until the recent discovery of the neural glymphatic system.  This highly specialized waste disposal network includes classical lymphatic vessels in the dura that absorb fluid and metabolic by-products and debris from the underlying cerebrospinal fluid (CSF) in the subarachnoid space. The subarachnoid space is continuous with the Virchow-Robin peri-arterial and peri-vascular spaces which surround the arteries and veins that penetrate into the neural tissue, respectively.  The dural lymphatic vessels exit the cranial vault via an anterior and a posterior route and eventually drain into the deep cervical lymph nodes. Aided by the presence of aquaporin 4 on the perivascular endfeet of astrocytes, nutrients and other molecules enter the brain from peri-arterial spaces and form interstitial fluid (ISF) that baths neurons and glia before being released into peri-venous spaces.  Melatonin, a pineal-derived secretory product which is in much higher concentration in the CSF than in the blood, is believed to follow this route and to clear waste products such as amyloid-β from the interstitial space. The clearance of amyloid-β reportedly occurs especially during slow wave sleep which happens concurrently with highest CSF levels of melatonin.  Experimentally, exogenously-administered melatonin defers amyloid-β buildup in the brain of animals and causes its accumulation in the cervical lymph nodes. Clinically, with increased age CSF melatonin levels decrease markedly, co-incident with neurodegeneration and dementia.  Collectively, these findings suggest a potential association between the loss of melatonin, decreased glymphatic drainage and neurocognitive decline in the elderly.

scholarly journals Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

2021 ◽  
Vol 15 ◽  
Author(s):  
Gianfranco Natale ◽  
Fiona Limanaqi ◽  
Carla L. Busceti ◽  
Federica Mastroiacovo ◽  
Ferdinando Nicoletti ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Lymphatic Vessels ◽  
Normal Pressure ◽  
Lymphatic Drainage ◽  
Brain Parenchyma ◽  
Waste Products ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Glymphatic Pathway ◽  
The Brain

The classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared of waste products. It was generally thought that clearance depends on cerebrospinal fluid (CSF). Not long ago, an anatomically and functionally discrete paravascular space was revised to provide a pathway for the clearance of molecules drained within the interstitial space. According to this model, CSF enters the brain parenchyma along arterial paravascular spaces. Once mixed with interstitial fluid and solutes in a process mediated by aquaporin-4, CSF exits through the extracellular space along venous paravascular spaces, thus being removed from the brain. This process includes the participation of perivascular glial cells due to a sieving effect of their end-feet. Such draining space resembles the peripheral lymphatic system, therefore, the term “glymphatic” (glial-lymphatic) pathway has been coined. Specific studies focused on the potential role of the glymphatic pathway in healthy and pathological conditions, including neurodegenerative diseases. This mainly concerns Alzheimer’s disease (AD), as well as hemorrhagic and ischemic neurovascular disorders; other acute degenerative processes, such as normal pressure hydrocephalus or traumatic brain injury are involved as well. Novel morphological and functional investigations also suggested alternative models to drain molecules through perivascular pathways, which enriched our insight of homeostatic processes within neural microenvironment. Under the light of these considerations, the present article aims to discuss recent findings and concepts on nervous lymphatic drainage and blood–brain barrier (BBB) in an attempt to understand how peripheral pathological conditions may be detrimental to the CNS, paving the way to neurodegeneration.

scholarly journals The brain’sglymphatic system:physiological anatomy and clinical perspectives

2018 ◽  
Vol 10 (4) ◽  
pp. 94-100 ◽  
Author(s):  
V. N. Nikolenko ◽  
M. V. Oganesyan ◽  
N. N. Yakhno ◽  
E. A. Orlov ◽  
E. E. Porubayeva ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Cerebral Arteries ◽  
Lymphatic Vessels ◽  
Circulatory System ◽  
Brain Parenchyma ◽  
Special Role ◽  
Close Link ◽  
New Therapeutic Approaches ◽  
The Central Nervous System ◽  
The Brain

The recently discovered glymphatic system (GS) ensures the efficient clearance of interstitial fluid and soluble compounds from the central nervous system into cerebrospinal fluid (CSF), which compensates for the lack of conventional lymphatic vessels in the brain parenchyma. This unique anatomical and physiological phenomenon had been unknown until 2012. GS lacks inherent proper vessels Р the current of CSF and interstitial fluid is carried out directly inside the arterial walls (the perivascular pathway) or near the walls of the cerebral arteries and veins (the paravascular pathway). Current biorheological technologies could establish a special role of aquaporin-4 in the filtration of CSF and interstitial fluid. The close link between GS and the CSF circulatory system allows the established views on fluid dynamics within the brain to be reconsidered. The discovery of GS can contribute to our understanding of the pathogenesis of increased intracranial pressure and neurodegenerative diseases, as well as to the elaboration of new therapeutic approaches to their treatment.

Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide1

2002 ◽  
Vol 227 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Weihong Pan ◽  
Beka Solomon ◽  
Lawrence M. Maness ◽  
Abba J. Kastin
Keyword(s):  
Ex Vivo ◽  
Amyloid Β ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Blocking Antibodies ◽  
The Brain

Amyloid-β peptides (Aβ) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Aβ outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Aβ have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Aβ in the peripheral blood, block the passage of Aβ across the BBB, or prevent Aβ deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aβ (125I-Aβ1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aβ after iv bolus injection. It also significantly decreased the accumulation of Aβ in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Aβ1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aβ into the brain after perfusion. Therefore, effective antibodies to Aβ can reduce the influx of Aβ1-40 into the brain.

scholarly journals Brain lymphatic drainage system – visualization opportunities and current state of the art

2020 ◽  
Vol 9 (3) ◽  
pp. 81-89
Author(s):  
G. S. Yankova ◽  
O. B. Bogomyakova
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Lymphatic Drainage ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.

scholarly journals Distribution of Suramin, an Antitrypanosomal Drug, across the Blood-Brain and Blood-Cerebrospinal Fluid Interfaces in Wild-Type and P-Glycoprotein Transporter-Deficient Mice

2007 ◽  
Vol 51 (9) ◽  
pp. 3136-3146 ◽  
Author(s):  
Lisa Sanderson ◽  
Adil Khan ◽  
Sarah Thomas
Keyword(s):  
Choroid Plexus ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Sleeping Sickness ◽  
New Drugs ◽  
Wild Type ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Targeted Mutation ◽  
The Brain

ABSTRACT Although 60 million people are exposed to human African trypanosomiasis, drug companies have not been interested in developing new drugs due to the lack of financial reward. No new drugs will be available for several years. A clearer understanding of the distribution of existing drugs into the brains of sleeping sickness patients is needed if we are to use the treatments that are available more safely and effectively. This proposal addresses this issue by using established animal models. Using in situ brain perfusion and isolated incubated choroid plexus techniques, we investigated the distribution of [3H]suramin into the central nervous systems (CNSs) of male BALB/c, FVB (wild-type), and P-glycoprotein-deficient (Mdr1a/Mdr1b-targeted mutation) mice. There was no difference in the [3H]suramin distributions between the three strains of mice. [3H]suramin had a distribution similar to that of the vascular marker, [14C]sucrose, into the regions of the brain parenchyma that have a blood-brain barrier. However, the association of [3H]suramin with the circumventricular organ samples, including the choroid plexus, was higher than that of [14C]sucrose. The association of [3H]suramin with the choroid plexus was also sensitive to phenylarsine oxide, an inhibitor of endocytosis. The distribution of [3H]suramin to the brain was not affected by the presence of other antitrypanosomal drugs or the P-glycoprotein efflux transporter. Overall, the results confirm that [3H]suramin would be unlikely to treat the second or CNS stage of sleeping sickness.

How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 806-812 ◽  
Author(s):  
Eric Hatterer ◽  
Nathalie Davoust ◽  
Marianne Didier-Bazes ◽  
Carine Vuaillat ◽  
Christophe Malcus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Subventricular Zone ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Cervical Lymph Nodes ◽  
The Central Nervous System ◽  
Anatomic Feature

AbstractThe lack of draining lymphatic vessels in the central nervous system (CNS) contributes to the so-called “CNS immune privilege.” However, despite such a unique anatomic feature, dendritic cells (DCs) are able to migrate from the CNS to cervical lymph nodes through a yet unknown pathway. In this report, labeled bone marrow-derived myeloid DCs were injected stereotaxically into the cerebrospinal fluid (CSF) or brain parenchyma of normal rats. We found that DCs injected within brain parenchyma migrate little from their site of injection and do not reach cervical lymph nodes. In contrast, intra-CSF-injected DCs either reach cervical lymph nodes or, for a minority of them, infiltrate the subventricular zone, where neural stem cells reside. Surprisingly, DCs that reach cervical lymph nodes preferentially target B-cell follicles rather than T-cell-rich areas. This report sheds a new light on the specific role exerted by CSF-infiltrating DCs in the control of CNS-targeted immune responses. (Blood. 2006; 107:806-812)

scholarly journals Waste Clearance in the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Jasleen Kaur ◽  
Lara M. Fahmy ◽  
Esmaeil Davoodi-Bojd ◽  
Li Zhang ◽  
Guangliang Ding ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Perivascular Spaces ◽  
Future Directions ◽  
Relevant Role ◽  
Healthy Functioning ◽  
The Brain ◽  
Brain Homeostasis

Waste clearance (WC) is an essential process for brain homeostasis, which is required for the proper and healthy functioning of all cerebrovascular and parenchymal brain cells. This review features our current understanding of brain WC, both within and external to the brain parenchyma. We describe the interplay of the blood-brain barrier (BBB), interstitial fluid (ISF), and perivascular spaces within the brain parenchyma for brain WC directly into the blood and/or cerebrospinal fluid (CSF). We also discuss the relevant role of the CSF and its exit routes in mediating WC. Recent discoveries of the glymphatic system and meningeal lymphatic vessels, and their relevance to brain WC are highlighted. Controversies related to brain WC research and potential future directions are presented.

scholarly journals Cerebrospinal Fluid and Interstitial Fluid Motion via the Glymphatic Pathway Modelled by Optimal Mass Transport

2016 ◽  
Author(s):  
Vadim Ratner ◽  
Yi Gao ◽  
Hedok Lee ◽  
Maikan Nedergaard ◽  
Helene Benveniste ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Interstitial Fluid ◽  
Initial Conditions ◽  
Fluid Motion ◽  
Flow Patterns ◽  
Brain Parenchyma ◽  
Fluid Exchange ◽  
Waste Products ◽  
Glymphatic Pathway ◽  
The Brain

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the `glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs [1,2]. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through peri-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach [3] to model the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data.

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