Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging–Guided Focused Ultrasound–Induced Blood–Brain Barrier Opening in a Mouse Glioblastoma Model

dc.contributor.author

Zhang, Yanrong

dc.contributor.author

Wang, Jing

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Ghobadi, Sara Natasha

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Zhou, Haiyan

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Huang, Ai

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Gerosa, Marco

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Hou, Qingyi

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Keunen, Olivier

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Golebiewska, Anna

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Habte, Frezghi G

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Grant, Gerald A

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Paulmurugan, Ramasamy

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Lee, Kevin S

dc.contributor.author

Wintermark, Max

dc.date.accessioned

2023-04-10T18:14:58Z

dc.date.available

2023-04-10T18:14:58Z

dc.date.issued

2023-01-01

dc.date.updated

2023-04-10T18:14:58Z

dc.description.abstract

An orthotopically allografted mouse GL26 glioma model (Ccr2RFP/wt–Cx3cr1GFP/wt) was used to evaluate the effect of transient, focal opening of the blood–brain barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB opening was induced by magnetic resonance imaging (MRI)–guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not exhibit significant changes in cell numbers when compared with tumors in animals not receiving FUS. However, tumors that received two or three sessions of MRgFUS had significantly increased amounts of both CX3CR1-GFP and CCR2-RFP cells. The effect of MRgFUS on immune cell composition was also characterized and quantified using flow cytometry. Glioma implantation resulted in increased amounts of lymphocytes, monocytes and neutrophils in the brain parenchyma. Tumors administered MRgFUS exhibited increased numbers of monocytes and monocyte-derived TAMs. In addition, MRgFUS-treated tumors exhibited more CD80+ cells in monocytes and microglia. In summary, transient, focal opening of the BBB using MRgFUS combined with microbubbles can activate the homing and differentiation of monocytes and induce a shift toward a more pro-inflammatory status of the immune environment in glioblastoma.

dc.identifier.issn

0301-5629

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1879-291X

dc.identifier.uri

https://hdl.handle.net/10161/27031

dc.language

en

dc.publisher

Elsevier BV

dc.relation.ispartof

Ultrasound in Medicine and Biology

dc.relation.isversionof

10.1016/j.ultrasmedbio.2022.12.006

dc.title

Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging–Guided Focused Ultrasound–Induced Blood–Brain Barrier Opening in a Mouse Glioblastoma Model

dc.type

Journal article

duke.contributor.orcid

Grant, Gerald A|0000-0002-2651-4603

pubs.begin-page

1082

pubs.end-page

1090

pubs.issue

5

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

pubs.organisational-group

Neurobiology

pubs.organisational-group

Duke Cancer Institute

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Neurosurgery

pubs.publication-status

Published

pubs.volume

49

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