Using focused ultrasound to modulate microglial structure and function

Sarina Grewal; Elisa Gonçalves de Andrade; Rikke Hahn Kofoed; Paul M Matthews; Isabelle Aubert; Marie-Ève Tremblay; Sophie V Morse

doi:10.3389/fncel.2023.1290628

Using focused ultrasound to modulate microglial structure and function

Front Cell Neurosci. 2023 Dec 18:17:1290628. doi: 10.3389/fncel.2023.1290628. eCollection 2023.

Authors

Sarina Grewal^#^{1

2}, Elisa Gonçalves de Andrade^#^{3

4}, Rikke Hahn Kofoed^{5

6

7}, Paul M Matthews^{2

8}, Isabelle Aubert^{7

9}, Marie-Ève Tremblay^{4

10

11

12}, Sophie V Morse^{1

8}

Affiliations

¹ Department of Bioengineering, Imperial College London, London, United Kingdom.
² Department of Brain Sciences, Imperial College London, London, United Kingdom.
³ Neuroscience Graduate Program, Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
⁴ Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
⁵ Department of Neurosurgery, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁶ Center for Experimental Neuroscience-CENSE, Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
⁷ Hurvitz Brain Sciences Research Program, Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
⁸ UK Dementia Research Institute, Imperial College London, London, United Kingdom.
⁹ Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
¹¹ Department of Molecular Medicine, Université Laval, Québec, QC, Canada.
¹² Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.

^# Contributed equally.

Abstract

Transcranial focused ultrasound (FUS) has the unique ability to target regions of the brain with high spatial precision, in a minimally invasive manner. Neuromodulation studies have shown that FUS can excite or inhibit neuronal activity, demonstrating its tremendous potential to improve the outcome of neurological diseases. Recent evidence has also shed light on the emerging promise that FUS has, with and without the use of intravenously injected microbubbles, in modulating the blood-brain barrier and the immune cells of the brain. As the resident immune cells of the central nervous system, microglia are at the forefront of the brain's maintenance and immune defense. Notably, microglia are highly dynamic and continuously survey the brain parenchyma by extending and retracting their processes. This surveillance activity aids microglia in performing key physiological functions required for brain activity and plasticity. In response to stressors, microglia rapidly alter their cellular and molecular profile to help facilitate a return to homeostasis. While the underlying mechanisms by which both FUS and FUS + microbubbles modify microglial structure and function remain largely unknown, several studies in adult mice have reported changes in the expression of the microglia/macrophage marker ionized calcium binding adaptor molecule 1, and in their phagocytosis, notably of protein aggregates, such as amyloid beta. In this review, we discuss the demonstrated and putative biological effects of FUS and FUS + microbubbles in modulating microglial activities, with an emphasis on the key cellular and molecular changes observed in vitro and in vivo across models of brain health and disease. Understanding how this innovative technology can modulate microglia paves the way for future therapeutic strategies aimed to promote beneficial physiological microglial roles, and prevent or treat maladaptive responses.

Keywords: blood-brain barrier; focused ultrasound; functional effects; glia; microglia; modulation; neurodegeneration.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program (M-ÈT is a Tier 2 Canada Research Chair in Neurobiology of Aging and Cognition and IA is a Tier 1 Canada Research Chair in Brain Repair and Regeneration). SVM acknowledges funding from Imperial College London, through the Imperial College Research Fellowship grant. PMM acknowledges the generous support from the Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme. PMM and SVM acknowledge support from the UK Dementia Research Institute which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. RK acknowledges funding from the Reintegration fellowship from Carlsberg Foundation (CF22-1463).