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Gepubliceerd: vrijdag 12 september 2014 10:34

PubMed - "Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined."

" (...) results indicated that the structure of the BBB was damaged and the permeability of ions and low-molecular-weight molecules was increased."

Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure

Wang LF, Li X, Gao YB, Wang SM, Zhao L, Dong J, Yao BW, Xu XP, Chang GM, Zhou HM, Hu XJ, Peng RY. Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure. Mol Neurobiol. 2014 Sep 9. [Epub ahead of print]

Abstract

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined.

An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm2, 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined.

Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation.

Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

Excerpts

... Cells from the exposed group were subjected to microwaves for 5 min with a mean power density of 50 mW/cm² at a frequency of 2.856 GHz ... The microwave pulses were delivered at 500 pps, respectively, with a pulse width of 500 ns. The peak field power density tested with a calibrated detector and an oscilloscope for the exposed group was 200 W/cm². Cells from the sham-treated control group underwent the same conditions, but the microwave generators were not energized ...

The BBB prevents the free passage of various molecules from the blood into the CNS. Previous studies have shown that exposure to microwaves can increase the permeability of the BBB to small molecules such as sucrose, Evans-Blue dye, lanthanum nitrate, and albumin [21, 23, 24]. Although these studies have focused mainly on thermal effects, microwaves also exert non-thermal effects on the BBB. In our study, the microwave exposure to BBB was non-thermal since no temperature change occurred in the culture medium. However, there were still some negative effects and found that the BBB permeability did not change after exposure to low-power 2,450 MHz and 1,439 Hz continuous waves, 1.8 GHz and 915 MHz pulses and continuous waves [25–28] ...

In the current study, we established an in vitro BBB model using the epithelial/endothelial-like human ECV304 cell line and primary astrocytes ...

... results indicated that the structure of the BBB was damaged and the permeability of ions and low-molecular-weight molecules was increased.