Determining the role of mechanical stimuli in blood-brain barrier opening
The blood-brain barrier (BBB) shields the brain from potentially harmful substances and forms a vital separation layer between the cerebral compartment and the circulatory system. While its integrity is essential to sustaining cerebral homeostasis and for brain survival, it also inhibits the transfer of most large molecules, thus severely limiting the usability of systemically administered drugs.
A treatment using microbubbles (MBs) in combination with focused ultrasound (FUS) has been proposed  to bypass the BBB in a non-invasive, transient and spatially confined way. The comportment of these MBs inside capillary blood vessels when exposed to FUS has been studied by means of computational modeling (Figure 1). Numerical results  indicate a significant increase in wall shear stress (WSS) and pressure as well as their respective spatial gradients in the affected vasculature. The goal of this project is the experimental assessment of biomechanical effects of such loading in an in vitro BBB model.
We will design and set up an experiment capable of monitoring the change of BBB permeability due to exposure to high frequency mechanical stresses. This setup will consist of an in vitro cerebral endothelial cell layer (Figure. 2), utilities to create oscillating WSS and pressure stimuli and assets to monitor the permeability of the BBB and measure the applied mechanical stresses (Figure. 3). We aim to separate the impacts of pressure, WSS and their respective spatial gradients to identify the most prominent factor. The final system shall allow for microscopic visualization of BBB permeability and relate it to the magnitude and type of applied mechanical stimulus.
This project brings together competences in cell biology, biochemistry, micro engineering and physics and will serve to advance the knowledge on the process of mechanically induced BBB opening.
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- Wiedemair W et al. On ultrasound-induced microbubble oscillation in a capillary blood vessel and its implications for the blood-brain barrier Phys. Med. Biol. 57 1019-45 (2012)