Transcranial Direct Current Stimulation Transiently Increases Solute Transport in Brain Tissue

Abstract

IntroductionTranscranial direct current stimulation (tDCS) is a non‐invasive electrical stimulation investigated to treat a broad range of brain disorders and to enhance memory and cognition in healthy individuals. Our prior study has shown that tDCS with proper dosage can achieve non‐invasive and temporary increase in the blood‐brain barrier (BBB) permeability (P). To further investigate whether tDCS also increases the material transport in brain tissue, we employed high resolution multiphoton microscopy to collect the spreading images of fluorescently‐labeled solutes in the rat brain tissue after tDCS treatment. The effective solute diffusion coefficient in the brain tissue (Deff ) was determined by using our previously developed method. Deff is a quantitative indicator for solute transport in a medium.MethodsAfter 20 min 1 mA tDCS treatment, sodium fluorescein (MW 376), or FITC‐dextran 70k in 1% BSA mammalian Ringer was injected into the rat (SD, 250–300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. Simultaneously, the 3‐D images of a post‐capillary vessel and its surrounding area in the rat brain tissue 100–200 mm below the pia mater were collected by laser scanning multiphoton microscopy with 820 nm excitation wavelength. The cerebral microvessel permeability (P) and the effective solute diffusion coefficient in the brain tissue Deff were determined from the rate of dye spreading images. Specifically, Deff was estimated by curve fitting the spatio‐temporal solute concentration (fluorescence intensity) distribution by using an unsteady diffusion transport model.Results and DiscussionIt was found that in 5–10 min post 20 min–1mA tDCS, Deff/Dfree increases from 0.45 to 0.50 for sodium fluorescein (n=5) and from 0.11 to 0.25 for dextran 70k (n=6), all the increased Deff returned to the control level in 25–30 min post tDCS. tDCS indeed transiently makes the brain tissue less restrictive to solute transport, especially for larger solutes.ConclusionstDCS not only transiently increases the BBB permeability but also enhances the solute transport in brain tissue.Support or Funding InformationSupported by NIH RO1 NS101362‐01