Abstract
The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (Deff) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, Deff increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in Deff returned to the control level 25–30 min post tDCS. A mathematical model for Deff in the extracelluar space (ECS) further predicts that this dose of tDCS increases Deff by transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies.
Highlights
The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation suggests a generalizable mechanism of action
Our findings suggest that Transcranial direct current stimulation (tDCS) can be used as a non-invasive, tolerated, and low-cost approach for the enhancement of the brain drug delivery, especially macromolecules, delivered through the B BB23 or C SF46
A customized high-resolution multiphoton microscopy system was used to image the spread across rat brain tissue of fluorescently-labeled solutes following their injection through the carotid artery in response to tDCS or under control conditions
Summary
The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. 5–10 min post 20 min–1 mA tDCS, Deff increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. The objective of the current study is to test if tDCS modulates the ECS, as measurable by substance transport in brain tissue, and as distinguishable from additional effects increasing the BBB permeability. We used a small solute, sodium fluorescein (MW 376), and two large solutes, BSA (bovine serum album, MW ~ 69k) with negative charge (charge number − 19) and Dex-70k with no charge as the representative test substances and quantified their effective diffusion coefficients Deff in rat brain tissue under control and in response to tDCS treatments. We used a small solute, sodium fluorescein (MW 376), and two large solutes, BSA (bovine serum album, MW ~ 69k) with negative charge (charge number − 19) and Dex-70k with no charge as the representative test substances and quantified their effective diffusion coefficients Deff in rat brain tissue under control and in response to tDCS treatments. Deff is a quantitative indicator for substance transport in porous media, such as brain tissue
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
