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Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices

Author

Listed:
  • Amira Sayed Hanafy

    (University Hospital Bonn
    University of Bonn)

  • Pia Steinlein

    (University Hospital Bonn
    University of Bonn)

  • Julika Pitsch

    (University Hospital Bonn
    University Hospital Bonn)

  • Mariella Hurtado Silva

    (The University of Sydney)

  • Natascha Vana

    (University Hospital Bonn)

  • Albert J. Becker

    (University Hospital Bonn)

  • Mark Evan Graham

    (The University of Sydney)

  • Susanne Schoch

    (University Hospital Bonn)

  • Alf Lamprecht

    (University of Bonn)

  • Dirk Dietrich

    (University Hospital Bonn)

Abstract

The blood-brain barrier (BBB) is a tightly and actively regulated vascular barrier. Answering fundamental biological and translational questions about the BBB with currently available approaches is hampered by a trade-off between accessibility and biological validity. We report an approach combining micropipette-based local perfusion of capillaries in acute brain slices with multiphoton microscopy. Micro-perfusion offers control over the luminal solution and allows application of molecules and drug delivery systems, whereas the bath solution defines the extracellular milieu in the brain parenchyma. Here we show, that this combination allows monitoring of BBB transport at the cellular level, visualization of BBB permeation of cells and molecules in real-time and resolves subcellular details of the neurovascular unit. In combination with electrophysiology, it permits comparison of drug effects on neuronal activity following luminal versus parenchymal application. We further apply micro-perfusion to the human and mouse BBB of epileptic hippocampi highlighting its utility for translational research and analysis of therapeutic strategies.

Suggested Citation

  • Amira Sayed Hanafy & Pia Steinlein & Julika Pitsch & Mariella Hurtado Silva & Natascha Vana & Albert J. Becker & Mark Evan Graham & Susanne Schoch & Alf Lamprecht & Dirk Dietrich, 2023. "Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36070-6
    DOI: 10.1038/s41467-023-36070-6
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    References listed on IDEAS

    as
    1. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabeth Ra, 2018. "Author Correction: A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 560(7716), pages 3-3, August.
    2. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Del Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabet, 2018. "A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 554(7693), pages 475-480, February.
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