Controlled electroporation of the blood-brain barrier

BPJ_110_2_3C_v2Brain endothelial cells are the major constituent of the blood-brain barrier (BBB) and permeability is the key to successful drug delivery across the BBB. The BBB regulates the transport of different substances from blood to the brain by moving through the cell (transcellular transport) or between the cells (paracellular transport). However, it is considered an obstacle to efficient delivery of drugs that target the central nervous system.

Pulsed electric fields are one of several methods that have the potential to temporarily make the BBB permeable when substances are traveling through the transcellular or paracellular pathways.  The electroporation phenomenon is mainly responsible for opening the cell membrane and enhancing the transcellular pathway across the BBB. Therefore, in order to get a more accurate picture of this transport phenomenon, it is necessary to investigate the effect of electropermeabilization on the endothelial cell monolayer of the BBB.

For transcellular transport to occur, molecules are first absorbed through the apical side of the cell membrane into the cytoplasm, and then they pass through to the basolateral side. Therefore, monitoring cellular absorbtion provides insight into possible enhancement of transcellular transport for different substances and can help us determine whether or not a certain treatment is effective in transporting drugs across the BBB.

The cover image shows the permeabilization of the brain endothelial cell monolayer at different sections of the tapered microfluidic channel, which is implemented in this study as a platform for delivering the pulsed electric fields. The electric pulses were applied at the channel ends, making a gradient of electric field across the channel which is inversely proportional to the channel width. Therefore the electropermeabilization could be monitored for a range of electric field magnitudes in a single experiment. The cells were initially stained in green using calcein AM and then pulsed in the presence of propidium iodide (PI), which is naturally impermeable to the cells. Upon entering the cell, PI stains the cell nuclei red, making it a valid probe for monitoring absorption. The images are taken using an inverted fluorescent microscope with two filters which enable the visualization of red and green stains.

The results from varying pulse strengths and the number of applied pulses may provide information that can be used to find the proper parameters to enhance transcellular transport across the BBB using pulsed electric fields without causing any permanent damage.

– Mohammad Bonakdar, Elisa Wasson, Yong Woo Lee and Rafael Davalos

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