Ultrasound frequency-controlled microbubble dynamics in brain vessels regulate the enrichment of inflammatory pathways in the blood-brain barrier
Microbubble-enhanced ultrasound provides a noninvasive physical method to locally overcome major obstacles to the accumulation of blood-borne therapeutics in the brain, posed by the blood-brain barrier (BBB). However, due to the highly nonlinear and coupled behavior of microbubble dynamics in brain vessels, the impact of microbubble resonant effects on BBB signaling and function remains undefined. Here, combined theoretical and prospective experimental investigations reveal that microbubble resonant effects in brain capillaries can control the enrichment of inflammatory pathways that are sensitive to wall shear stress and promote differential expression of a range of transcripts in the BBB, supporting the notion that microbubble dynamics exerted mechanical stress can be used to establish molecular, in addition to spatial, therapeutic windows to target brain diseases. Consistent with these findings, a robust increase in cytotoxic T-cell accumulation in brain tumors was observed, demonstrating the functional relevance and potential clinical significance of the observed immuno-mechano-biological responses.
Authors
- Costas Arvanitis (ORCID: https://orcid.org/0000-0002-7737-1446)
- Miguel O. Bernabéu (ORCID: https://orcid.org/0000-0002-6456-3756)
- Hanjoong Jo (ORCID: https://orcid.org/0000-0003-1833-372X)
- Chulyong Kim (ORCID: https://orcid.org/0009-0000-7550-0980)
- C.-S. Park (ORCID: https://orcid.org/0000-0002-3975-1202)
- Hideho Okada (ORCID: https://orcid.org/0000-0003-0076-9920)
- Hohyun Lee (ORCID: https://orcid.org/0000-0002-7939-6751)
- Pavlina Chuntova (ORCID: https://orcid.org/0000-0002-5356-9909)
- Akane Yamamichi (ORCID: https://orcid.org/0000-0002-8141-7339)
- Marco Gallus (ORCID: https://orcid.org/0009-0007-4954-8420)
- Yutong Guo (ORCID: https://orcid.org/0000-0002-3712-8353)
Institutions
- Georgia Institute of Technology (US)
- Emory University (US)
- The Wallace H. Coulter Department of Biomedical Engineering (US)
- Parker Institute for Cancer Immunotherapy (US)
- Neurological Surgery (US)
- The Queen's Medical Research Institute (GB)
- Stanford University (US)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s41467-024-52329-y
- Citations
- 45
- Primary Topic
- Ultrasound and Hyperthermia Applications
- Type
- article
- Field-Weighted Citation Impact
- 8.30
Funders
- Focused Ultrasound Foundation
- Parker Institute for Cancer Immunotherapy
- Deutsche Forschungsgemeinschaft
- Fondation Leducq
- National Institutes of Health
- Engineering and Physical Sciences Research Council
- National Heart, Lung, and Blood Institute
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke