Inhibition of Nitric Oxide Synthase (NOS) by NG‐monomethyl‐L‐arginine (L‐NMMA) Reduces Transient Increase in the Blood‐Brain Barrier Solute Permeability in Rat Brain by Transcranial Direct Current Stimulation

Abstract

Transcranial Direct Current Stimulation (tDCS) is a non‐invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Our prior study has shown that tDCS with proper dosage can achieve non‐invasive, selective and temporary increase in the blood‐brain barrier (BBB) permeability (P). To further investigate the cellular and structural mechanisms by which tDCS increases P, prior to 20 min 1 mA tDCS, we pretreated the cerebral microvessels for ~30 min with a NOS inhibitor, L‐NMMA, through the tail vein injection, at an initial blood concentration of ~1 mM. We then used laser scanning multiphoton microscopy with 840 nm excitation wavelength to determine P of the cerebral microvessels in the rat brain tissue 100–200 μm below the pia mater. 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. P were determined from the rate of dye spreading images around individual microvessels in the brain tissue. It was found that L‐NMMA pretreatment significantly reduced the increased P to sodium fluorescein from ~13‐fold to ~4‐fold of its control, and P to Dextran‐70k from ~88‐fold to ~8‐fold of its control at 5 min post tDCS treatment. Treatment by L‐NMMA alone for ~55 min significantly decreased the P to both solutes to ~66% of their controls. The predictions from our previously developed mathematical model for the BBB suggested that increasing the cleft width between adjacent endothelial cells and the width of basement membrane between the endothelium and astrocyte foot processes, due to contracting of endothelial cells, should be responsible for the transient increase in P by tDCS. In contrast, pretreatment of L‐NMMA may strengthen the structural components, most likely the junction strands in the cleft between endothelial cells to prevent the permeability increase by tDCS.Support or Funding InformationNIH RO1 NS101362‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.