Characterization of the responses of brain macrophages to focused ultrasound-mediated blood-brain barrier opening

被引：22

作者：

Kline-Schoder, Alina R. ^{[1
]}

Chintamen, Sana ^{[2
]}

Willner, Moshe J. ^{[3
]}

Dibenedetto, Melody R. ^{[1
]}

Noel, Rebecca L. ^{[1
]}

Batts, Alec J. ^{[1
]}

Kwon, Nancy ^{[1
]}

Zacharoulis, Stergios ^{[4
]}

Wu, Cheng-Chia ^{[4
]}

Menon, Vilas ^{[5
]}

Kernie, Steven G. ^{[4
]}

Konofagou, Elisa E. ^{[1
,6
]}

机构：

[1] Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA

[2] Columbia Univ, Dept Neurobiol & Behav, New York, NY USA

[3] Columbia Univ, Vagelos Coll Phys & Surg, New York, NY USA

[4] Columbia Univ, Dept Pediat, New York, NY USA

[5] Columbia Univ, Dept Neurol, New York, NY USA

[6] Columbia Univ, Dept Radiol, New York, NY 10032 USA

来源：

NATURE BIOMEDICAL ENGINEERING | 2024年 / 8卷 / 05期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

MOUSE MODEL; INFLAMMATORY RESPONSE; MYELOID SUBSETS; MICROGLIA; DISEASE; CELLS; HIPPOCAMPUS; DISTINCT;

D O I：

10.1038/s41551-023-01107-0

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The opening of the blood-brain barrier (BBB) by focused ultrasound (FUS) coupled with intravenously injected microbubbles can be leveraged as a form of immunotherapy for the treatment of neurodegenerative disorders. However, how FUS BBB opening affects brain macrophages is not well understood. Here by using single-cell sequencing to characterize the distinct responses of microglia and central nervous system-associated macrophages (CAMs) to FUS-mediated BBB opening in mice, we show that the treatment remodels the immune landscape via the recruitment of CAMs and the proliferation of microglia and via population size increases in disease-associated microglia. Both microglia and CAMs showed early and late increases in population sizes, yet only the proliferation of microglia increased at both timepoints. The population of disease-associated microglia also increased, accompanied by the upregulation of genes associated with gliogenesis and phagocytosis, with the depletion of brain macrophages significantly decreasing the duration of BBB opening.

引用

页码：650 / 663

页数：17

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