Insights into cerebral haemodynamics and oxygenation utilising <i>in vivo</i> mural cell imaging and mathematical modelling

Sweeney, Paul W.; Walker‐Samuel, Simon; Shipley, Rebecca J.

doi:10.1101/195503

Cited by 6 publications

(12 citation statements)

References 43 publications

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“…This is in line with the expression of α-smooth muscle actin in mural cells of up to 4 th branch order vessels as seen by immunohistochemistry staining and the use of transgenic animals (Hartmann et al, 2015a, Hill et al, 2015. In recent computational and experimental works, these vascular segments have also been shown to be the location of blood flow regulation to supply a particular downstream region (Sweeney et al, 2018, Grubb et al, 2019. It is likely that many findings regarding pericyte control of blood flow were based on experiments focusing on EPs (Peppiatt et al, 2006.…”

Section: Discussionsupporting

confidence: 58%

Distinct signatures of calcium activity in brain pericytes

Glück

Ferrari

Keller

et al. 2020

Preprint

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Even though pericytes have been implicated in various neurological disorders, little is known about their function and signaling pathways in the healthy brain. Here, we characterized cortical pericyte calcium dynamics using two-photon imaging of Pdgfrβ-CreERT2;GCaMP6s mice under anesthesia in vivo and in brain slices ex vivo. We found distinct differences between pericyte subtypes in vivo: Ensheathing pericytes exhibited smooth muscle cell-like calcium dynamics, while calcium signals in capillary pericytes were irregular, higher in frequency and occurred in cellular microdomains. In contrast to ensheathing pericytes, capillary pericytes retained their spontaneous calcium signals during prolonged anesthesia and in the absence of blood flow ex vivo. Chemogenetic activation of neurons in vivo and acute increase of extracellular potassium in brain slices strongly decreased calcium activity in capillary pericytes. We propose that neuronal activity-induced elevations in extracellular potassium suppress calcium activity in capillary pericytes, likely mediated by Kir2.2 and KATP channel activation.

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Section: Discussionsupporting

confidence: 58%

Distinct signatures of calcium activity in brain pericytes

Glück

Ferrari

Keller

et al. 2020

Preprint

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“…In this contribution, oxygen transport both in the preexisting and in the NV is included through the mass balance equations and , respectively. However, in our TCAT framework, the primary variable is the mass fraction of oxygen instead of oxygen concentrations per unit volume of plasma or tissue

C^{n \overset{α}{true}} false[ml {normalO}_{2} false/ ml false]

or oxygen partial pressures

P_{oxy}^{α} false[mmHg false]

as commonly used for oxygen transport models . Hence, we need to convert mass fractions to partial pressures in order to reuse the mass transfer relations which are normally applied.…”

Section: Incorporation Of the Embedded 1d Fluid Network Into The Vascmentioning

confidence: 99%

“…Furthermore, H D is the discharge hematocrit, that is, the volume flux of red blood cells divided by total blood volume flux and

C_{0}^{n \overset{v}{true}}

the concentration of oxygen at maximum saturation. We do not consider a heterogeneous distribution of hematocrit due to diverging bifurcations as in other numerical models but constant discharge hematocrit, see Table . For the binding of oxygen to hemoglobin, the Hill equation

S ((), P_{oxy}^{v}) = \frac{{((), P_{oxy}^{v})}^{n}}{{((), P_{oxy}^{v})}^{n} + {((), P_{oxy,50}^{v})}^{n}}

is typically applied.…”

Section: Incorporation Of the Embedded 1d Fluid Network Into The Vascmentioning

confidence: 99%

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An approach for vascular tumor growth based on a hybrid embedded/homogenized treatment of the vasculature within a multiphase porous medium model

Kremheller

Vuong

Schrefler

et al. 2019

Numer Methods Biomed Eng

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The aim of this work is to develop a novel computational approach to facilitate the modeling of angiogenesis during tumor growth. The preexisting vasculature is modeled as a 1D inclusion and embedded into the 3D tissue through a suitable coupling method, which allows for nonmatching meshes in 1D and 3D domain. The neovasculature, which is formed during angiogenesis, is represented in a homogenized way as a phase in our multiphase porous medium system. This splitting of models is motivated by the highly complex morphology, physiology, and flow patterns in the neovasculature, which are challenging and computationally expensive to resolve with a discrete, 1D angiogenesis and blood flow model. Moreover, it is questionable if a discrete representation generates any useful additional insight. By contrast, our model may be classified as a hybrid vascular multiphase tumor growth model in the sense that a discrete, 1D representation of the preexisting vasculature is coupled with a continuum model describing angiogenesis. It is based on an originally avascular model which has been derived via the thermodynamically constrained averaging theory. The new model enables us to study mass transport from the preexisting vasculature into the neovasculature and tumor tissue. We show by means of several illustrative examples that it is indeed capable of reproducing important aspects of vascular tumor growth phenomenologically.

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“…15 Pericyte contractility, or the modulation of microvessel diameter, is an area of ongoing investigation, particularly in the central nervous system (CNS). [16][17][18][19][20][21][22][23] In addition, the tissue regeneration capacity of pericytes, acting as a pool of perivascular mesenchymal stem cells, [24][25][26] has also been described as a potential role for these cells. [27][28][29] This particular role may be context-and/or model-dependent however.…”

mentioning

confidence: 99%

The pericyte microenvironment during vascular development

et al. 2019

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Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.

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Insights into cerebral haemodynamics and oxygenation utilising in vivo mural cell imaging and mathematical modelling

Cited by 6 publications

References 43 publications

Distinct signatures of calcium activity in brain pericytes

Distinct signatures of calcium activity in brain pericytes

An approach for vascular tumor growth based on a hybrid embedded/homogenized treatment of the vasculature within a multiphase porous medium model

The pericyte microenvironment during vascular development

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