scholarly journals Fluid dynamics of cerebrospinal fluid flow in perivascular spaces

2019 ◽  
Vol 16 (159) ◽  
pp. 20190572 ◽  
Author(s):  
John H. Thomas
Keyword(s):  
Fluid Dynamics ◽  
Cerebrospinal Fluid ◽  
Dynamic Models ◽  
Fluid Dynamic ◽  
Critical Evaluation ◽  
Amyloid Β ◽  
Perivascular Spaces ◽  
Waste Products ◽  
Basic Fluid ◽  
The Brain

The flow of cerebrospinal fluid along perivascular spaces (PVSs) is an important part of the brain’s system for delivering nutrients and eliminating metabolic waste products (such as amyloid-β); it also offers a pathway for the delivery of therapeutic drugs to the brain parenchyma. Recent experimental results have resolved several important questions about this flow, setting the stage for advances in our understanding of its fluid dynamics. This review summarizes the new experimental evidence and provides a critical evaluation of previous fluid-dynamic models of flows in PVSs. The review also discusses some basic fluid-dynamic concepts relevant to these flows, including the combined effects of diffusion and advection in clearing solutes from the brain.

scholarly journals Surface periarterial spaces of the mouse brain are open, not porous

2020 ◽  
Vol 17 (172) ◽  
pp. 20200593 ◽  
Author(s):  
Fatima Min Rivas ◽  
Jia Liu ◽  
Benjamin C. Martell ◽  
Ting Du ◽  
Humberto Mestre ◽  
...  
Keyword(s):  
Porous Medium ◽  
Viscous Flow ◽  
Hydraulic Resistance ◽  
Dynamic Models ◽  
Fluid Dynamic ◽  
Perivascular Spaces ◽  
Waste Products ◽  
Solid Obstacles ◽  
The Brain ◽  
Open Nature

Fluid-dynamic models of the flow of cerebrospinal fluid in the brain have treated the perivascular spaces either as open (without internal solid obstacles) or as porous. Here, we present experimental evidence that pial (surface) periarterial spaces in mice are essentially open. (1) Paths of particles in the perivascular spaces are smooth, as expected for viscous flow in an open vessel, not diffusive, as expected for flow in a porous medium. (2) Time-averaged velocity profiles in periarterial spaces agree closely with theoretical profiles for viscous flow in realistic models, but not with the nearly uniform profiles expected for porous medium. Because these spaces are open, they have much lower hydraulic resistance than if they were porous. To demonstrate, we compute hydraulic resistance for realistic periarterial spaces, both open and porous, and show that the resistance of the porous spaces are greater, typically by a factor of a hundred or more. The open nature of these periarterial spaces allows significantly greater flow rates and more efficient removal of metabolic waste products.

scholarly journals Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer’s and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

2020 ◽  
pp. 1-24
Author(s):  
Conrad N. Trumbore
Keyword(s):  
Cerebrospinal Fluid ◽  
Conformational Changes ◽  
Extensional Flow ◽  
Amyloid Β ◽  
High Energy ◽  
Mechanical Agitation ◽  
Cerebrospinal Fluid Flow ◽  
Pulse Waves ◽  
Amyloid Diseases ◽  
The Brain

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

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 Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals Cerebrospinal fluid influx drives acute ischemic tissue swelling

Science ◽  
2020 ◽  
Vol 367 (6483) ◽  
pp. eaax7171 ◽  
Author(s):  
Humberto Mestre ◽  
Ting Du ◽  
Amanda M. Sweeney ◽  
Guojun Liu ◽  
Andrew J. Samson ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Perivascular Spaces ◽  
Fluid Accumulation ◽  
Multiphoton Imaging ◽  
Flow Channels ◽  
Ischemic Tissue ◽  
The Brain ◽  
Vascular Compartment

Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.

Fluid Dynamics

2017 ◽  
pp. 94-139
Keyword(s):  
Fluid Dynamics ◽  
Pressure Drop ◽  
Static Loading ◽  
Fluid Dynamic ◽  
Transition To Turbulence ◽  
Viscous Effects ◽  
Basic Fluid ◽  
Free Shear Layers ◽  
Present Context ◽  
Loss Coefficients

A review of basic fluid dynamics is presented in this chapter. Fluid static loading of hydraulic gates is examined. The focus in the present context will be on one-dimensional, incompressible flow of Newtonian fluids (air and water). Viscous effects will be included as loss coefficients in pressure drop calculations through ducts and channels. Discharge coefficients of hydraulics gates are presented to account for viscous effects in the flow past these gates. More advanced concepts related to the instabilities of boundary layers and free shear layers, and transition to turbulence will be introduced briefly and references provided for further investigation by the interested reader. Readers are encouraged to review additional fluid dynamic concepts using the text with which they are most comfortable.

In Vivo Microdialysis in Mice Captures Changes in Alzheimer’s Disease Cerebrospinal Fluid Biomarkers Consistent with Developing Pathology

2021 ◽  
pp. 1-14
Author(s):  
Christiana Bjorkli ◽  
Claire Louet ◽  
Trude Helen Flo ◽  
Mary Hemler ◽  
Axel Sandvig ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Mouse Model ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Intracerebral Microdialysis ◽  
Preclinical Models ◽  
The Brain

Background: Preclinical models of Alzheimer’s disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-β (Aβ) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal CSF monitoring. Objective: An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Here we draw upon patient-based findings to characterize CSF biomarkers in a commonly used preclinical mouse model for AD. Methods: Our modified push-pull microdialysis method was first validated ex vivo with human CSF samples, and then in vivo in an AD mouse model, permitting assessment of dynamic changes of CSF Aβ and tau and allowing for better translational understanding of CSF biomarkers. Results: We demonstrate that CSF biomarker changes in preclinical models capture what is observed in the brain; with a decrease in CSF Aβ observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain parenchyma. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of Aβ and tau, comparable to CSF collection by lumbar puncture in patients. Conclusion: Our approach can further advance AD and other neurodegenerative research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal and can additionally be used to administer pharmaceutical compounds and assess their efficacy (Bjorkli, unpublished data).

scholarly journals Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Science ◽  
2019 ◽  
Vol 366 (6465) ◽  
pp. 628-631 ◽  
Author(s):  
Nina E. Fultz ◽  
Giorgio Bonmassar ◽  
Kawin Setsompop ◽  
Robert A. Stickgold ◽  
Bruce R. Rosen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Function ◽  
Slow Waves ◽  
Neural Dynamics ◽  
Rapid Eye Movement Sleep ◽  
Csf Flow ◽  
Csf Dynamics ◽  
Macroscopic Scale ◽  
Waste Products ◽  
The Brain

Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non–rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.

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