Application of Pulsed Electric Fields to Gating Blood-Brain Barrier for Drug Delivery
Document Type
Abstract
Publication Date
11-7-2024
DOI
10.25776/2p5j-9m24
Abstract
The blood-brain barrier (BBB) serves as a protective layer separating the blood circulation from neural tissue. It is crucial for preserving the delicate extracellular environment within the neuronal parenchyma. Neuroinflammatory events can disrupt the BBB by affecting adherens junctions (AJs) and tight junctions (TJs). The BBB presents a significant obstacle for drug delivery to the central nervous system (CNS). It is composed of a continuous layer of specialized endothelial cells connected by tight junctions, along with pericytes, a no fenestrated basal lamina, and astrocytic foot processes. VE-cadherin, a key component of the vascular system, is particularly essential for the formation of AJs and the overall structure of the BBB. This intricate barrier regulates and restricts the entry of therapeutics into the CNS. Various innovative approaches have been investigated to improve the transport of therapeutics across the BBB, each offering distinct benefits and drawbacks. We hypothesized that application of pulsed electric fields could open the BBB for drug delivery.
Human microvascular endothelial cells were grown as monolayers to 90% confluence on 8-well plates. They were pulsed with 15-50 electrical pulses (EP) of 100 μsec duration, frequency of 1 Hz, and applied electric field 200-1000 V. Four hours later the cells were fixed, permeabilized and immunostained for visualization of VE-Cadherin. Control groups included unpulsed cells, as well as cells pulsed with 15 pulses of 200 V (100 μsec duration, frequency of 1 Hz); both control groups exhibited physiologically normal expression of VE-cadherin. Endothelial cells, pulsed with 15 EP at 500 and 1000 V (100 μsec duration, frequency of 1 Hz) demonstrated reduction in VE-Cadherin immunostaining, indicative of endothelial barrier disruption. Additionally, 50 EP at 500 V completely disrupted the endothelial barrier. This data suggests that microsecond EP affect VE-Cadherin expression. Additional studies are needed to understand the mechanisms behind these observations.
Repository Citation
Solopov, Pavel A.; Guo, Siqi; Xiao, Shu; and Catravas, John D., "Application of Pulsed Electric Fields to Gating Blood-Brain Barrier for Drug Delivery" (2024). 2024 Frank Reidy Research Center for Bioelectrics Retreat. 8.
https://digitalcommons.odu.edu/bioelectrics-2024retreat/8
