Effect of high frequency electromagnetic field on blood brain barrier permeability

Increasing the permeability of the blood-brain barrier (BBB) in a controlled and selective manner in clinical applications can lead to advantageous outcomes such as accelerating the antidepressant effects, which typically have a delayed response, without causing sedative effects. This study aims to determine the appropriate duration of 27,12 MHz radiofrequency electromagnetic field (RF EMF) application to enhance BBB permeability without damaging it. Additionally, the roles and effects of enzymes and proteins in this process are investigated. In studies on the effects of the 27,12 MHz RF-PEMF, a non-invasive treatment method we used in the study, it has been shown to particularly enhance tissue oxygenation and thereby accelerate tissue regeneration. In our study, which involved twenty-four adult Wistar Albino female rats, the rats were divided into four groups. The groups were arranged to be exposed to RF PEMF for 30 minutes, 180 minutes, and 360 minutes, as well as a control group. Applications were performed in an experimental setup designed for RF-PEMF exposure at 10 V/m. Post-exposure, brain and cerebellum tissues were removed under general anesthesia, and parts of these tissues were collected for staining and immunohistochemical (CD31, Haptoglobin) analysis. Other parts were preserved for Biochemical Analyses of Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI), and genetic analyses of Interleukin-6 (IL-6), Hypoxia-Inducible Factor-1 Alpha (HIF-1α), Endothelial Nitric Oxide Synthase (eNOS), Claudin-1, and Occludin. Microscopic examination of brain and cerebellum tissues revealed no lesions in the control group, whereas mild hyperemia and edema were observed in the other groups depending on the exposure duration. Examination of haptoglobin immunostained sections showed mild expressions in the cerebellum only in the groups exposed for 180 minutes and 360 minutes. HIF-1α levels increased more in the 360-minute group compared to the 30-minute group, but eNOS expressions were highest in the 30-minute RF-EMF group. Claudin-1 expressions significantly decreased in the 180-minute and 360-minute RF-EMF groups, while Occludin levels significantly decreased in all three groups. vi This study demonstrates that 27,12 MHz RF-EMF applications can increase BBB permeability when applied for different durations and that this effect is mediated through the eNOS pathway. It is concluded that keeping the application duration short may provide a potential advantage in increasing BBB permeability without damaging its structure.