Acute exposure to 27.12 MHz radiofrequency electromagnetic field disrupts blood-brain barrier integrity via eNOS activation and occludin down-regulation.

Objectives: Controlled modulation of blood-brain barrier (BBB) permeability without inducing damage represents a promising strategy for enhancing central nervous system drug delivery. Materials and Methods: This study investigated the effects of 27.12 MHz radiofrequency electromagnetic field (RF-EMF) exposure for 30, 180, and 360 min on BBB integrity in female Wistar rats (n=6 per group). Brain and cerebellar tissues were analyzed histologically and immunohistochemically (haptoglobin, CD31), and molecular analyses were performed for oxidative stress parameters (TAS, TOS, and OSI), inflammatory and hypoxia markers (IL-6 and HIF-1α), endothelial nitric oxide synthase (eNOS), and tight junction proteins (claudin-1 and occludin). Results: RF-EMF exposure for 30 min significantly increased eNOS gene expression without triggering oxidative stress or inflammation. Longer exposures (180 and 360 min) resulted in increased HIF-1α expression, decreased levels of claudin-1 and occludin, and histopathological signs of hyperemia and edema, particularly in the cerebellar tissue. Notably, occludin expression decreased in all exposure groups, while eNOS was maximally up-regulated at 30 min. Conclusion: Thirty-minute RF-EMF exposure at 27.12 MHz transiently modulates BBB permeability via eNOS activation and occludin down-regulation without apparent tissue damage. These findings suggest that short-term RF-EMF application may serve as a non-invasive tool for targeted BBB modulation. Further studies are warranted to refine exposure parameters and assess translational potential in neuropharmacological applications.