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  1. Article: The elusive brain perivascular fibroblast: a potential role in vascular stability and homeostasis.

    Sosa, Maria J / Shih, Andy Y / Bonney, Stephanie K

    Frontiers in cardiovascular medicine

    2023  Volume 10, Page(s) 1283434

    Abstract: In the brain, perivascular fibroblasts (PVFs) reside within the perivascular spaces (PVSs) of arterioles and large venules, however their physiological and pathophysiological roles remain largely unknown. PVFs express numerous extracellular matrix ... ...

    Abstract In the brain, perivascular fibroblasts (PVFs) reside within the perivascular spaces (PVSs) of arterioles and large venules, however their physiological and pathophysiological roles remain largely unknown. PVFs express numerous extracellular matrix proteins that are found in the basement membrane and PVS surrounding large diameter vessels. PVFs are sandwiched between the mural cell layer and astrocytic endfeet, where they are poised to interact with mural cells, perivascular macrophages, and astrocytes. We draw connections between the more well-studied PVF pro-fibrotic response in ischemic injury and the less understood thickening of the vascular wall and enlargement of the PVS described in dementia and neurodegenerative diseases. We postulate that PVFs may be responsible for stability and homeostasis of the brain vasculature, and may also contribute to changes within the PVS during disease.
    Language English
    Publishing date 2023-11-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2023.1283434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.

    Bonney, Stephanie K / Nielson, Cara D / Sosa, Maria J / Shih, Andy Y

    bioRxiv : the preprint server for biology

    2023  

    Abstract: In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. ... ...

    Abstract In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a hallmark of many neurological disorders and how this web is engaged during vascular damage remains unknown. We performed
    Significance: Deterioration of the capillary network is a characteristic of many neurological diseases and can exacerbate neuronal dysfunction and degeneration due to poor blood perfusion. Here we show that focal capillary injuries can induce vessel regression and elicit sustained vasoconstriction in upstream transitional vessels that branch from cortical penetrating arterioles. This reduces blood flow to broader, uninjured regions of the same microvascular network. These findings suggest that widespread and cumulative damage to brain capillaries in neurological disease may broadly affect blood supply and contribute to hypoperfusion through their remote actions.
    Language English
    Publishing date 2023-11-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.28.564529
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Corrigendum:

    Nielson, Cara D / Berthiaume, Andrée-Anne / Bonney, Stephanie K / Shih, Andy Y

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 974311

    Abstract: This corrects the article DOI: 10.3389/fnins.2022.900761.]. ...

    Abstract [This corrects the article DOI: 10.3389/fnins.2022.900761.].
    Language English
    Publishing date 2022-07-12
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.974311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Differential Effects of Retinoic Acid Concentrations in Regulating Blood-Brain Barrier Properties.

    Bonney, Stephanie / Siegenthaler, Julie A

    eNeuro

    2017  Volume 4, Issue 3

    Abstract: The blood-brain barrier (BBB) is a multifaceted property of the brain vasculature that protects the brain and maintains homeostasis by tightly regulating the flux of ions, molecules, and cells across the vasculature. Blood vessels in the brain are formed ...

    Abstract The blood-brain barrier (BBB) is a multifaceted property of the brain vasculature that protects the brain and maintains homeostasis by tightly regulating the flux of ions, molecules, and cells across the vasculature. Blood vessels in the brain are formed by endothelial cells that acquire barrier properties, such as tight and adherens junctions, soon after the brain vasculature is formed. Endothelial WNT signaling is crucial to induce these BBB properties by regulating their expression and stabilization. Recent studies have implicated retinoic acid (RA) signaling in BBB development and shown that pharmacological concentrations of RA (≥5 µm) can induce BBB properties in cultured brain endothelial cells. However, a recent study demonstrated that RA inhibits endothelial WNT signaling during brain development, suggesting that RA does not promote BBB properties. We therefore investigated whether RA plays a physiological role in BBB development. We found that BBB function and junctional protein expression was unaffected in mouse mutants that have a reduced capacity to synthesize RA (
    MeSH term(s) Alcohol Oxidoreductases/genetics ; Alcohol Oxidoreductases/metabolism ; Animals ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/growth & development ; Blood-Brain Barrier/metabolism ; Cell Line, Tumor ; Dietary Supplements ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Gene Expression/drug effects ; Immunoblotting ; Immunohistochemistry ; Liver X Receptors/metabolism ; Mice, Transgenic ; Polymerase Chain Reaction ; Retinoid X Receptors/metabolism ; Tretinoin/administration & dosage ; Tretinoin/metabolism
    Chemical Substances Liver X Receptors ; Retinoid X Receptors ; Tretinoin (5688UTC01R) ; Alcohol Oxidoreductases (EC 1.1.-) ; trans-retinol dehydrogenase (EC 1.1.1.-)
    Language English
    Publishing date 2017-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0378-16.2017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Endothelial structure contributes to heterogeneity in brain capillary diameter.

    Sargent, Sheridan M / Bonney, Stephanie K / Li, Yuandong / Stamenkovic, Stefan / Takeno, Marc M / Coelho-Santos, Vanessa / Shih, Andy Y

    Vascular biology (Bristol, England)

    2023  Volume 5, Issue 1

    Abstract: The high metabolic demand of brain tissue is supported by a constant supply of blood flow through dense microvascular networks. Capillaries are the smallest class of vessels in the brain and their lumens vary in diameter between ~2 and 5 μm. This ... ...

    Abstract The high metabolic demand of brain tissue is supported by a constant supply of blood flow through dense microvascular networks. Capillaries are the smallest class of vessels in the brain and their lumens vary in diameter between ~2 and 5 μm. This diameter range plays a significant role in optimizing blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if the architecture of the endothelial wall also contributes to capillary diameter. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical mm3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of two to six interlocked endothelial cells, while the capillaries intervening these zones are composed of either one or two endothelial cells, with roughly equal proportions. The luminal area and diameter are on average slightly larger with capillary segments composed of two interlocked endothelial cells vs one endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, including pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.
    Language English
    Publishing date 2023-09-06
    Publishing country England
    Document type Journal Article
    ISSN 2516-5658
    ISSN (online) 2516-5658
    DOI 10.1530/VB-23-0010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Meningeal origins and dynamics of perivascular fibroblast development on the mouse cerebral vasculature.

    Jones, Hannah E / Coelho-Santos, Vanessa / Bonney, Stephanie K / Abrams, Kelsey A / Shih, Andy Y / Siegenthaler, Julie A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs drive fibrosis following injury but their homeostatic functions are not well detailed. ...

    Abstract Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs drive fibrosis following injury but their homeostatic functions are not well detailed. In mice, PVFs were previously shown to be absent from most brain regions at birth and are only detected postnatally within the cerebral cortex. However, the origin, timing, and cellular mechanisms of PVF development are not known. We used
    Summary: Brain perivascular fibroblasts migrate from their origin in the meninges and proliferate locally to fully cover penetrating vessels during postnatal mouse development.
    Language English
    Publishing date 2023-03-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.23.533982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Endothelial structure contributes to heterogeneity in brain capillary diameter.

    Sargent, Sheridan M / Bonney, Stephanie K / Li, Yuandong / Stamenkovic, Stefan / Takeno, Marc / Coelho-Santos, Vanessa / Shih, Andy Y

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The high metabolic demand of brain tissue is supported by a constant supply of blood through dense microvascular networks. Capillaries are the smallest class of vessels and vary in diameter between ∼2 to 5 μm in the brain. This diameter range plays a ... ...

    Abstract The high metabolic demand of brain tissue is supported by a constant supply of blood through dense microvascular networks. Capillaries are the smallest class of vessels and vary in diameter between ∼2 to 5 μm in the brain. This diameter range plays a significant role in the optimization of blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if endothelial wall architecture also contributes to capillary diameter heterogeneity. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical MM^3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of 2 to 5 interlocked endothelial cells, while the numerous capillary segments intervening these zones are composed of either 1 or 2 endothelial cells, with roughly equal proportions. The luminal area and diameter is on average slightly larger with capillary segments composed of 2 interlocked endothelial cells versus 1 endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, such as pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.
    Language English
    Publishing date 2023-04-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.26.538503
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Meningeal origins and dynamics of perivascular fibroblast development on the mouse cerebral vasculature.

    Jones, Hannah E / Coelho-Santos, Vanessa / Bonney, Stephanie K / Abrams, Kelsey A / Shih, Andy Y / Siegenthaler, Julie A

    Development (Cambridge, England)

    2023  Volume 150, Issue 19

    Abstract: Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs contribute to fibrosis following injury but their homeostatic functions are not ... ...

    Abstract Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs contribute to fibrosis following injury but their homeostatic functions are not defined. PVFs were previously shown to be absent from most brain regions at birth and are only detected postnatally within the cerebral cortex. However, the origin, timing and cellular mechanisms of PVF development are not known. We used Col1a1-GFP and Col1a2-CreERT2 transgenic mice to track PVF development postnatally. Using lineage tracing and in vivo imaging we show that brain PVFs originate from the meninges and are first seen on parenchymal cerebrovasculature at postnatal day (P) 5. After P5, PVF coverage of the cerebrovasculature expands via local cell proliferation and migration from the meninges. Finally, we show that PVFs and perivascular macrophages develop concurrently. These findings provide the first complete timeline for PVF development in the brain, enabling future work into how PVF development is coordinated with cell types and structures in and around the perivascular spaces to support normal CNS vascular function.
    Language English
    Publishing date 2023-10-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.201805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Impaired drainage through capillary-venous networks contributes to age-related white matter loss.

    Stamenkovic, Stefan / Schmid, Franca / Weitermann, Nicolas / Takasaki, Kevin / Bonney, Stephanie K / Sosa, Maria J / Li, Yuandong / Bennett, Hannah C / Kim, Yongsoo / Waters, Jack / Shih, Andy Y

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We ... ...

    Abstract The gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We used
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.11.579849
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Distinct features of brain perivascular fibroblasts and mural cells revealed by

    Bonney, Stephanie K / Sullivan, Liam T / Cherry, Timothy J / Daneman, Richard / Shih, Andy Y

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2021  Volume 42, Issue 6, Page(s) 966–978

    Abstract: Perivascular fibroblasts (PVFs) are recognized for their pro-fibrotic role in many central nervous system disorders. Like mural cells, PVFs surround blood vessels and express Pdgfrβ. However, these shared attributes hinder the ability to distinguish PVFs ...

    Abstract Perivascular fibroblasts (PVFs) are recognized for their pro-fibrotic role in many central nervous system disorders. Like mural cells, PVFs surround blood vessels and express Pdgfrβ. However, these shared attributes hinder the ability to distinguish PVFs from mural cells. We used
    MeSH term(s) Animals ; Brain/blood supply ; Capillaries/diagnostic imaging ; Fibroblasts/metabolism ; Mice ; Mice, Transgenic ; Pericytes/metabolism
    Language English
    Publishing date 2021-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X211068528
    Database MEDical Literature Analysis and Retrieval System OnLINE

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