scholarly journals Hydraulic resistance of perivascular spaces in the brain

2019 ◽  
Author(s):  
Jeffrey Tithof ◽  
Douglas H. Kelley ◽  
Humberto Mestre ◽  
Maiken Nedergaard ◽  
John H. Thomas
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Vessels ◽  
Hydraulic Resistance ◽  
Perivascular Spaces ◽  
Navier Stokes Equation ◽  
Pial Arteries ◽  
Cross Sectional ◽  
Annular Channels ◽  
The Brain

AbstractBackgroundPerivascular spaces (PVSs) are annular channels that surround blood vessels and carry cerebrospinal fluid through the brain, sweeping away metabolic waste. In vivo observations reveal that they are not concentric, circular annuli, however: the outer boundaries are often oblate, and the blood vessels that form the inner boundaries are often offset from the central axis.MethodsWe model PVS cross-sections as circles surrounded by ellipses and vary the radii of the circles, major and minor axes of the ellipses, and two-dimensional eccentricities of the circles with respect to the ellipses. For each shape, we solve the governing Navier-Stokes equation to determine the velocity profile for steady laminar flow and then compute the corresponding hydraulic resistance.ResultsWe find that the observed shapes of PVSs have lower hydraulic resistance than concentric, circular annuli of the same size, and therefore allow faster, more efficient flow of cerebrospinal fluid. We find that the minimum hydraulic resistance (and therefore maximum flow rate) for a given PVS cross-sectional area occurs when the ellipse is elongated and intersects the circle, dividing the PVS into two lobes, as is common around pial arteries. We also find that if both the inner and outer boundaries are nearly circular, the minimum hydraulic resistance occurs when the eccentricity is large, as is common around penetrating arteries.ConclusionsThe concentric circular annulus assumed in recent studies is not a good model of the shape of actual PVSs observed in vivo, and it greatly overestimates the hydraulic resistance of the PVS. Our parameterization can be used to incorporate more realistic resistances into hydraulic network models of flow of cerebrospinal fluid in the brain. Our results demonstrate that actual shapes observed in vivo are nearly optimal, in the sense of offering the least hydraulic resistance. This optimization may well represent an evolutionary adaptation that maximizes clearance of metabolic waste from the brain.

scholarly journals Cerebrospinal Fluid Efflux Through Dynamic Paracellular Pores on Venule as a Missing Piece for the Image of Brain Drainage System

2021 ◽  
Author(s):  
Yaqiong Dong ◽  
Ting Xu ◽  
Lan Yuan ◽  
Yahan Wang ◽  
Siwang Yu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Laser Scanning ◽  
Vascular Endothelial Cells ◽  
Drainage System ◽  
Fluorescein Isothiocyanate ◽  
Blood Pool ◽  
Confocal Laser ◽  
Perivascular Spaces ◽  
The Brain

Abstract Background: The glymphatic system has been considered to contribute to a larger portion of parenchyma waste clearance and related to pathogenesis of many neural degenerative diseases such as the Alzheimer’s disease (AD). However, up to date, the key route for the efflux from perivascular spaces to the blood pool remains a mystery.Methods: BBB-impermeable fluorescent lanthanide probes of different size were first applied as cerebrospinal fluid (CSF)/interstitial fluid (ISF) tracers to quantitatively clarify the relative importance of different pathways to drain CSF/ISF solutes. The in vivo dynamic flows of subarachnoid CSF labeled with fluorescein isothiocyanate-dextran (4 kDa) tracers along brain blood vessels were observed under a two-photon confocal laser scanning microscope. Results: Three phasic process for the brain drainage was observed, in which the rapid efflux of ISF solutes with a time constant close to the CSF oscillation during sleep appeals for new routes from perivenuous spaces to the blood pool. Careful observation on the dynamic efflux in vivo revealed a novel drainage pathway in which CSF molecules converge into the bloodstream directly through dynamic trumpet-like pores (basolateral f＜8 μm; apical f＜2 μm) on the wall of brain venule in mice. Zn2+, an inducer of reconstruction of the tight junctions (TJs) in vascular endothelial cells, could facilitate the brain clearance of macromolecular ISF solutes. Deficit clearance of Aβ through the asymmetric pores on venule potentially causing perivascular space dilation was observed on the AD model mice.Conclusions: The novel asymmetric pore path through reconstruction of endothelial TJs on the wall of venule shall provide a key piece for ISF solutes to drainage from brain in very rapid pathway. The update image would help to understand the structure and the regulation of glymphatic clearance of brain metabolites such as Aβ in search for the solutions of neurodegenerative diseases.

scholarly journals Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Aditya Raghunandan ◽  
Antonio Ladron-de-Guevara ◽  
Jeffrey Tithof ◽  
Humberto Mestre ◽  
Ting Du ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bulk Flow ◽  
Driving Mechanism ◽  
Perivascular Spaces ◽  
Pial Arteries ◽  
Waste Products ◽  
In Vivo Experiments ◽  
Tracer Particles ◽  
Syringe Injection

Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain’s mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna (CM) of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the CM using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection.

Microvascular features that suggest effectors of blood-flow regulation in the brain: Evidence by SEM of corrosion casts of intracerebral vessels

1990 ◽  
Vol 48 (3) ◽  
pp. 274-275
Author(s):  
Enrico D.F. Motti ◽  
Hans-Georg Imhof ◽  
Gazi M. Yasargil
Keyword(s):  
Blood Flow ◽  
Perfusion Pressure ◽  
Corrosion Casts ◽  
Cerebral Microcirculation ◽  
Pial Arteries ◽  
Random Occurrence ◽  
Brain Arteries ◽  
Homogeneous Network ◽  
The Brain

Physiologists have devoted most attention in the cerebrovascular tree to the arterial side of the circulation which has been subdivided in three levels: 1) major brain arteries which keep microcirculation constant despite changes in perfusion pressure; 2) pial arteries supposed to be effectors regulating microcirculation; 3) intracerebral arteries supposed to be deprived of active cerebral blood flow regulating devices.The morphological search for microvascular effectors in the cerebrovascular bed has been elusive. The opaque substance of the brain confines in vivo investigation to the superficial pial arteries. Most morphologists had to limit their observation to the random occurrence of a favorable site in the practically two-dimensional thickness of diaphanized histological sections. It is then not surprising most investigators of the cerebral microcirculation refer to an homogeneous network of microvessels interposed between arterioles and venules.We have taken advantage of the excellent depth of focus afforded by the scanning electron microscope (SEM) to investigate corrosion casts obtained injecting a range of experimental animals with a modified Batson's acrylic mixture.

scholarly journals The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1833
Author(s):  
Shannon Morgan McCabe ◽  
Ningning Zhao
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Blood Circulation ◽  
Critical Role ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013077
Author(s):  
Corey W Bown ◽  
Roxana O Carare ◽  
Matthew S Schrag ◽  
Angela L Jefferson
Keyword(s):  
Fluid Transport ◽  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Small Vessel ◽  
Aging Brain ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Clinical Consequences ◽  
The Brain

Perivascular spaces (PVS) are fluid filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on magnetic resonance imaging. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as two possible mechanisms that drive ePVS formation. In this review, we describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the two most prominent theoretical views and review ePVS associations with other common small vessel disease markers. As ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer’s disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

Perivascular (Virchow–Robin) spaces

2021 ◽  
pp. 86-89
Keyword(s):  
Blood Vessels ◽  
Shape Change ◽  
Lymphatic Drainage ◽  
Brain Regions ◽  
Mechanical Trauma ◽  
Normal Brain ◽  
Perivascular Spaces ◽  
Mr Images ◽  
Lenticulostriate Artery ◽  
The Brain

Perivascular spaces; also known as the Virchow-Robin Spaces, they are pleurally lined, interstitial fluid-filled areas that surround certain blood vessels in various organs, especially the perforating arteries in the brain, with an immunological function. Dilated perivascular spaces are divided into three types. The first of these is on the lenticulostriate artery, the second is in the cortex following the path of the medullary artery, and the third is in the midbrain. Perivascular spaces can be detected as areas of dilatation on MR images. Although a limited number of perivascular spaces can be seen in a normal brain, the increase in the number of these spaces has been associated with the incidence of various neurodegenerative diseases. Different theories have been suggested about the tendency of the perivascular spaces to expand. Current theories include mechanical trauma due to cerebrospinal fluid pulsing, elongation of penetrating blood vessels, unusual vascular permeability, and increased fluid exudation. In addition, the brain tissue atrophy that occurs with aging; It is thought to contribute to the widening of perivascular spaces by causing shrinkage of arteries, altered arterial wall permeability, obstruction of lymphatic drainage pathways and vascular demyelination. It is assumed that the clinical significance of the dilation tendencies of the perivascular spaces is based on shape change rather than size. These spaces have been mostly observed in brain regions such as corpus callosum, cingulate gyrus, dentate nucleus, substantia nigra and various arterial basins including lenticulostriate artery and mesencephalothalamic artery. In conclusion, when sections are taken on MR imaging, it is possible that perivascular spaces may be confused with microvascular diseases and some neurodegenerative changes. In addition, perivascular spaces can be seen without pathological significance. Therefore, it would be appropriate to investigate the etiological relationship by evaluating the radiological findings and clinical picture together.

Imaging

2017 ◽  
Author(s):  
Robert Laureno
Keyword(s):  
Resonance Imaging ◽  
Cross Sectional ◽  
Advantages And Disadvantages ◽  
Mri Scans ◽  
Cross Sectional Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Cellular Pathology ◽  
Brain And Spinal Cord ◽  
The Brain

This chapter on “Imaging” examines the relative advantages and disadvantages of computed tomography (CT) and magnetic resonance imaging (MRI) scans. It compares the modalities to each other and to gross neuropathology. For several decades, neurologists have been able to view cross-sectional images of living patients. Analogous to gross neuropathology, cross-sectional imaging displays the brain as an entire organ but does not demonstrate microscopic tissue or cellular pathology. By allowing practitioners to view sections of brain and spinal cord in vivo, imaging has improved neurologic practice and facilitated clinical research. This chapter deals with imaging topics that are important to the neurologist. The timing of scans, the effects of gravity, and the importance of plane of section are considered. Imaging is compared to gross neuropathology, and MRI is compared to CT.

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.

scholarly journals Endothelial Claudin

1999 ◽  
Vol 147 (1) ◽  
pp. 185-194 ◽  
Author(s):  
Kazumasa Morita ◽  
Hiroyuki Sasaki ◽  
Mikio Furuse ◽  
Shoichiro Tsukita
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Blood Vessels ◽  
Polyclonal Antibody ◽  
Polyclonal Antibodies ◽  
Transmembrane Protein ◽  
Velo Cardio Facial Syndrome ◽  
The Brain ◽  
Specific Polyclonal Antibody

Tight junctions (TJs) in endothelial cells are thought to determine vascular permeability. Recently, claudin-1 to -15 were identified as major components of TJ strands. Among these, claudin-5 (also called transmembrane protein deleted in velo-cardio-facial syndrome [TMVCF]) was expressed ubiquitously, even in organs lacking epithelial tissues, suggesting the possible involvement of this claudin species in endothelial TJs. We then obtained a claudin-6–specific polyclonal antibody and a polyclonal antibody that recognized both claudin-5/TMVCF and claudin-6. In the brain and lung, immunofluorescence microscopy with these polyclonal antibodies showed that claudin-5/TMVCF was exclusively concentrated at cell–cell borders of endothelial cells of all segments of blood vessels, but not at those of epithelial cells. Immunoreplica electron microscopy revealed that claudin-5/TMVCF was a component of TJ strands. In contrast, in the kidney, the claudin-5/TMVCF signal was restricted to endothelial cells of arteries, but was undetectable in those of veins and capillaries. In addition, in all other tissues we examined, claudin-5/TMVCF was specifically detected in endothelial cells of some segments of blood vessels, but not in epithelial cells. Furthermore, when claudin-5/TMVCF cDNA was introduced into mouse L fibroblasts, TJ strands were reconstituted that resembled those in endothelial cells in vivo, i.e., the extracellular face–associated TJs. These findings indicated that claudin-5/TMVCF is an endothelial cell–specific component of TJ strands.

scholarly journals Signs of Myelin Impairment in Cerebrospinal Fluid After Osmotic Opening of the Blood-Brain Barrier in Rats

2015 ◽  
pp. S603-S608 ◽  
Author(s):  
P. KOZLER ◽  
O. SOBEK ◽  
J. POKORNÝ
Keyword(s):  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Blood Brain Barrier ◽  
Basic Protein ◽  
Brain Barrier ◽  
In Vivo Experiment ◽  
Blood Brain ◽  
Significant Difference ◽  
The Brain

A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons.

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