Investigation of how stimulation intensity of rTMS affects magneto permeabilization of the Blood–Brain Barrier (BBB)

Abstract

ABSTRACT The present study aimed to assess the effect of the rTMS (repetitive Transcranial Magnetic Stimulation) intensity on the permeability of the BBB for brain-targeted drug delivery. For this purpose, different rTMS intensities including 70%, 100%, and 130% of Resting Motor Threshold (RMT) assessed in three groups of rats (three groups of 5 rats). Stimulation applied over the right hemisphere of the animals. The first phase of the study was composed of intravenous administration of Evans Blue Dye (EBD), rTMS stimulation and EBD uptake measurement in both brain hemispheres. The second examination was included rTMS stimulation, injection of the MRI Contrast Agent (CA), and signal intensity measurement in post-contrast images. Each exam also included five rats in a sham group. Thus, the total of 40 male Wistar rats enrolled in this study. There was no significant difference in the amount of EBD accumulated between the right hemisphere of the brain in the sham group and the group with 70% RMT magnetic stimulation, while this figure was significantly higher than the sham group for both 100 and 130% RMT groups. There was also a significant difference in this index between 100 and 130% groups. All of the results from the first phase of the study were consistent with the second assessment representing an upward trend of induced permeability by rising rTMS intensity. The results of this study imply that to cause an effective temporary disruption in the BBB the intensity of 100% RMT or above should be used for stimulation.