Ultrasound frequency-controlled microbubble dynamics in brain vessels regulate the enrichment of inflammatory pathways in the blood-brain barrier

Yutong Guo, Hohyun Lee, Chulyong Kim, Christian Park, Akane Yamamichi, Pavlina Chuntova, Marco Gallus, Miguel O. Bernabeu, Hideho Okada, Hanjoong Jo and Costas Arvanitis ()
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Yutong Guo: Woodruff School of Mechanical Engineering
Hohyun Lee: Woodruff School of Mechanical Engineering
Chulyong Kim: Woodruff School of Mechanical Engineering
Christian Park: Coulter Department of Biomedical Engineering
Akane Yamamichi: Department of Neurological Surgery
Pavlina Chuntova: Department of Neurological Surgery
Marco Gallus: Department of Neurological Surgery
Miguel O. Bernabeu: Usher Institute
Hideho Okada: Department of Neurological Surgery
Hanjoong Jo: Coulter Department of Biomedical Engineering
Costas Arvanitis: Woodruff School of Mechanical Engineering

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-52329-y

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