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

Authors

Yanrong Zhang
Jing Wang
Sara Natasha Ghobadi
Haiyan Zhou
Ai Huang
Marco Gerosa
Qingyi Hou
Olivier Keunen
Anna Golebiewska
Frezghi G Habte
Gerald A Grant
Ramasamy Paulmurugan
Kevin S Lee
Max Wintermark

Language

English

Publication Date

5-1-2023

Journal

Ultrasound in Medicine and Biology

DOI

10.1016/j.ultrasmedbio.2022.12.006

PMID

36717283

PMCID

PMC10059983

PubMedCentral® Posted Date

5-1-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

An orthotopically allografted mouse GL26 glioma model (Ccr2^RFP/wt-Cx3cr1^GFP/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 show significant changes in cell numbers when compared to tumors in animals not receiving FUS. However, tumors that received two or three sessions of MRgFUS showed significantly increased amounts of both CX3CR1-GFP and CCR2-RFP cells.

The effect of MRgFUS on immune cell composition was also characterized and quantified utilizing flow cytometry. Glioma implantation resulted in increased amounts of lymphocytes, monocytes, and neutrophils in the brain parenchyma. Tumors administered MRgFUS showed 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 towards a more proinflammatory status of the immune environment in glioblastoma.

Keywords

Mice, Animals, Blood-Brain Barrier, Glioblastoma, Microglia, Tumor-Associated Macrophages, Glioma, Disease Models, Animal, Magnetic Resonance Imaging, Microbubbles, Sterile inflammation, Glioblastoma, TAMs, microglia and macrophage activation, Focused Ultrasound, MRgFUS, microbubbles

Published Open-Access

yes

Recommended Citation

Zhang, Yanrong; Wang, Jing; Ghobadi, Sara Natasha; et al., "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" (2023). Faculty, Staff and Student Publications. 6651.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6651