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

Document Type : Original Article

Authors

1 Department of Bioengineering, Institute of Natural and Applied Sciences, Suleyman Demirel University, Isparta, Türkiye

2 Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Türkiye

3 Department of Genetics, Faculty of Medicine, Suleyman Demirel University, Isparta, Türkiye

4 Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Türkiye

5 Department of Anesthesia and Reanimation, Faculty of Medicine, Suleyman Demirel University, Isparta, Türkiye

6 Department of Electrical and Electronic Engineering, Suleyman Demirel University, Isparta, Türkiye

7 Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Türkiye

10.22038/ijbms.2025.86952.18784

Abstract

Objective(s): 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.

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Main Subjects


1. Segarra M, Aburto MR, Acker-Palmer A. Blood–brain barrier dynamics to maintain brain homeostasis. Trends Neurosci 2021; 44: 393-405.
2. Wu D, Chen Q, Chen X, Han F, Chen Z, Wang Y. The blood–brain barrier: Structure, regulation, and drug delivery. Signal Transduct Target Ther 2023; 8: 217-244.
3. Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood–brain barrier. Nat Rev Drug Discov 2021; 20: 362-383.
4. Rizk AA, Plitman E, Senthil P, Venkatraghavan L, Chowdhury T. Effects of anesthetic agents on blood brain barrier ıntegrity: A systematic review. Can J Neurol Sci 2023; 50: 897-904. 
5. Hashimoto Y, Campbell M. Tight junction modulation at the blood-brain barrier: Current and future perspectives. Biochim Biophys Acta Biomembr 2020; 1862: 183298-183309.
6. Lochhead JJ, Yang J, Ronaldson PT, Davis TP. Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders. Front Physiol 2020; 11:914-931.
7. Zhao X, Song S, Sun G, Strong R, Zhang J, Grotta JC, Aronowski J. Neuroprotective role of haptoglobin after intracerebral hemorrhage. J Neurosci 2009; 29: 15819-15827.
8. Wimmer I, Tietz S, Nishihara H, Deutsch U, Sallusto F, Gosselet F, et al. PECAM-1 stabilizes blood-brain barrier ıntegrity and favors paracellular T-cell diapedesis across the blood-brain barrier during neuroinflammation. Front Immunol 2019; 10: 711-728.
9. Kalinowska A, Losy J. PECAM-1, a key player in neuroinflammation. Eur J Neurol 2006; 13: 1284-1290.
10. Voirin AC, Chatard M, Briançon-Marjollet A, Pepin JL, Perek N, Roche F. Loss of blood-brain barrier ıntegrity in an ın vitro model subjected to ıntermittent hypoxia: ıs reversion possible with a hıf-1α pathway ınhibitor? Int J Mol Sci 2023; 24: 5062-5077.
11. Yang N, Yang X, Fang Y, Huang Y, Shi W, Li W, et al. Nitric oxide promotes cerebral ischemia/reperfusion injury through up-regulating hypoxia-inducible factor1-α-associated inflammation and apoptosis in rats. Neurosci Lett 2023; 795: 137034.
12. Thiel VE, Audus KL. Nitric oxide and blood–brain barrier integrity. Antioxid Redox Signal 2001; 3: 273-278.
13. Bushberg J, Chou C, Foster K, Kavet R, Maxson D, Tell R, Ziskin M. IEEE committee on man and radiation—COMAR technical information statement: Health and safety issues concerning exposure of the general public to electromagnetic energy from 5G wireless communications networks. Health Physics 2020; 119: 236-246. 
14. Bragin DE, Statom GL, Hagberg S, Nemoto EM. Increases in microvascular perfusion and tissue oxygenation via pulsed electromagnetic fields in the healthy rat brain. J Neurosurg 2015; 122: 1239-1247.
15. Taner R, Halil A, Uysal D, Sanem A, Ünlü Md, Oğuzoğlu As, et al. The Effects of combination of radiofrequency and pulsed magnetic field on carotid arteria ıschemia and reperfusion ınduced brain ınjury: A prelimınary report. Med J SDÜ 2023; 30: 630-642. 
16. Savran M, Ascı H, Erzurumlu Y, Ozmen O, Ilhan I, Sırın MC, et al. Theranekron: A novel anti-inflammatory candidate for acetic acid-induced colonic inflammation in rats. Mol Biol Rep 2022; 49: 8753-8760.
17. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277-285.
18. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-1111.
19. Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS 2020; 17: 69-93.
20. Konofagou EE, Tung YS, Choi J, Deffieux T, Baseri B, Vlachos F. Ultrasound-induced blood-brain barrier opening. Curr Pharm Biotechnol 2012; 13: 1332-1345.