Abstract
We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the applied current. A mathematical model based on a two-pore description of the endothelial transport barrier and a Helmholtz model of the electrical double layer describes the experimental data accurately and predicts enhanced significance of this mechanism in less permeable monolayers. This study demonstrates that DCS transiently alters the transport function of the BBB suggesting a new adjunct mechanism of tDCS.
Highlights
Transcranial direct current stimulation is being investigated for treatment of a broad range of neuropsychiatric disorders, as an adjunct to rehabilitation, and to facilitate cognitive performance in healthy individuals
After reestablishing the baseline for 3600 sec, direct current stimulation (DCS) was applied with the anode on top (t = 7200 sec) inducing an immediate increase in flux that persisted for the duration of DCS. (B) Average Jv as a function of time calculated from the raw data at intervals of 300 sec for n = 5 experiments performed as in (A)
We exposed bEnd.[3] monolayers grown on Transwell membranes to a low level of direct current of (1 mA) for 10 minutes and measured water and solute flux before, during, and after DCS
Summary
Transcranial direct current stimulation (tDCS) is being investigated for treatment of a broad range of neuropsychiatric disorders (e.g. depression, neuropathic pain, epilepsy1), as an adjunct to rehabilitation (e.g. stroke[2], traumatic brain injury3), and to facilitate cognitive performance in healthy individuals (e.g. accelerated learning[4]). A biophysical mechanism that could lead to transport of water and solutes across the BBB in response to an applied electric field is electroosmosis[19] This process derives from the movement of charged ions through small channels or pores that have fixed charge on their surface. To begin to address the possible role of the BBB in tDCS efficacy and safety, we applied 10 minutes of DCS characteristic of tDCS to monolayers of cultured ECs and measured their transport barrier responses. We found that DCS produced significant stimulation-polarity-specific fluid and solute movement across the EC layer that persisted only as long as the current was applied and was enhanced in cells with tighter junctions – all characteristic of the electroosmotic effect. A mathematical model based on a two pore description of the endothelial transport barrier and a Helmholtz model of the electrical double layer describes the experimental data accurately and predicts enhanced significance of this mechanism in tighter (less permeable) monolayers
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