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  3. Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions

Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions

  • Ultrason Sonochem. 2024 Jan 17:103:106768. doi: 10.1016/j.ultsonch.2024.106768.
Jifan Chen 1,  Jean-Michel Escoffre 2,  Oliver Romito 3,  Tarik Iazourene 2,  Antoine Presset 2,  Marie Roy 2,  Marie Potier Cartereau 3,  Christophe Vandier 3,  Yahua Wang 2,  Guowei Wang 4,  Pintong Huang 5,  Ayache Bouakaz 6
Affiliations

Affiliations

  • 1 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Zhejiang, China; Inserm UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
  • 2 Inserm UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
  • 3 Inserm UMR 1069 Nutrition, Croissance et Cancer (N2C), Faculté de Médecine, Université de Tours, F-37032, France.
  • 4 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Zhejiang, China.
  • 5 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Zhejiang, China; Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou 310053, China. Electronic address: [email protected].
  • 6 Inserm UMR 1253, iBrain, Université de Tours, Inserm, Tours, France. Electronic address: [email protected].
PMID: 38241945 DOI: 10.1016/j.ultsonch.2024.106768
Abstract

The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated. The aim of the study is to explore the contribution of transcytosis in the BBB transient opening using an in-vitro model of BBB. Utilizing a diverse set of techniques, including Ca2+ imaging, electron microscopy, and electrophysiological recordings, our results showed that the combined use of US and MBs triggers membrane deformation within the endothelial cell membrane, a phenomenon primarily observed in the US + MBs group. This deformation facilitates the vesicles transportation of 500 kDa fluorescent Dextran via dynamin-/caveolae-/clathrin- mediated transcytosis pathway. Simultaneously, we observed increase of cytosolic Ca2+ concentration, which is related with increased permeability of the 500 kDa fluorescent Dextran in-vitro. This was found to be associated with the Ca2+-protein kinase C (PKC) signaling pathway. The insights provided by the acoustically-mediated interaction between the microbubbles and the cells delineate potential mechanisms for macromolecular substance permeability.

Keywords

Blood-brain barrier; Bubble-cell mechanical interaction; Drug delivery; In-vitro; Macromolecular substance; Microbubbles; Transcytosis; Ultrasound.

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