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

**Authors:** Arzu Ulusoy, Halil Asci, Rumeysa Taner, Muhammet Yusuf Tepebasi, Ilter Ilhan, Pinar Karabacak, Selcuk Comlekci, Ozlem Ozmen

PMC · DOI: 10.22038/ijbms.2025.86952.18784 · Iranian Journal of Basic Medical Sciences · 2025-01-01

## TL;DR

Short exposure to a specific radiofrequency electromagnetic field temporarily changes the blood-brain barrier without causing damage, potentially aiding drug delivery to the brain.

## Contribution

Demonstrates that 30-minute exposure to 27.12 MHz RF-EMF transiently modulates BBB permeability via eNOS activation and occludin down-regulation.

## Key findings

- 30-minute RF-EMF exposure increased eNOS gene expression without oxidative stress or inflammation.
- Longer exposures caused HIF-1α upregulation, reduced claudin-1 and occludin, and histopathological changes.
- Occludin expression decreased in all exposure groups, with eNOS maximally up-regulated at 30 minutes.

## Abstract

Controlled modulation of blood-brain barrier (BBB) permeability without inducing damage represents a promising strategy for enhancing central nervous system drug delivery.

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).

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.

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.

## Linked entities

- **Genes:** NOS3 (nitric oxide synthase 3) [NCBI Gene 4846], IL6 (interleukin 6) [NCBI Gene 3569], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], CLDN7 (claudin 7) [NCBI Gene 1366], si:ch73-61d6.3 (uncharacterized si:ch73-61d6.3) [NCBI Gene 103182021]

## Full-text entities

- **Genes:** Nos3 (nitric oxide synthase 3) [NCBI Gene 24600] {aka eNos}, Pecam1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 29583] {aka CD31, Pecam}, Ocln (occludin) [NCBI Gene 83497], Cldn1 (claudin 1) [NCBI Gene 65129], Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Hp (haptoglobin) [NCBI Gene 24464] {aka Ba1-647}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}
- **Diseases:** inflammation (MESH:D007249), hyperemia (MESH:D006940), edema (MESH:D004487), hypoxia (MESH:D000860)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12829706/full.md

## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12829706/full.md

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Source: https://tomesphere.com/paper/PMC12829706