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Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultrasound Irradiation In Vitro

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Abstract

The research was conducted to study the increase of blood-tumor barrier (BTB) permeability through paracellular pathway by low-frequency ultrasound (LFU) irradiation in vitro. LFU (frequency = 1.0 MHz) was performed to irradiate BTB model from the co-culture of rat C6 glioma cells and rat brain microvascular endothelial cells (RBMECs). The permeability of BTB was measured by transendothelial electrical resistance (TEER) and flux of horseradish peroxidase (HRP) assays after LFU irradiation. Western-blotting, immunohistochemistry, and immunofluorescence assays were used to investigate the changes of expressions and distributions of tight junction (TJ)-associated proteins ZO-1, occludin, and claudin-5. The TEER value began to decrease, and the minimum value appeared at 2 h, then gradually returned to the original level at 24 h after LFU irradiation. With time, flux of HRP gradually increased and reached the peak 2 h after LFU irradiation. The expressions of ZO-1, occludin, and claudin-5 in RBMECs decreased, and decreased most significantly at 2 h, then gradually restored to the original level at 24 h. Meanwhile, they were discontinuously distributed in the cellular boundaries after LFU irradiation. In summary, the expresstion of TJ-associated proteins was down-regulated, TJ was opened, and the permeability of BTB was increased through paracellular pathway by LFU irradiation.

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Acknowledgment

This work was supported by the Natural Science Foundation of China, under contract No.30800451, No.30872656, No.30700861, No.30670723, and No.30973079; Scientific and Technological Research Projects in Colleges and Universities of Liaoning Province, No.2008850; the special fund for Scientific Research of Doctor-degree Subjects in Colleges and Universities, No.20092104110015; and Scientific and Technological Planning Projects of Shenyang, No.1072033-1-00 and No.1081266-9-00.

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Authors and Affiliations

  1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China

    Lilin Fan, Yunhui Liu & Haoqiang Ying

  2. Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China

    Zhen Zhang

  3. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, People’s Republic of China

    Yixue Xue, Ping Wang, Libo Liu & Hua Zhang

  4. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, 110001, People’s Republic of China

    Yixue Xue, Ping Wang, Libo Liu & Hua Zhang

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  1. Lilin Fan
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  2. Yunhui Liu
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  3. Haoqiang Ying
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  4. Yixue Xue
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  5. Zhen Zhang
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  6. Ping Wang
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  7. Libo Liu
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  8. Hua Zhang
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Corresponding author

Correspondence to Yunhui Liu.

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Lilin Fan and Yunhui Liu contributed equally to this work.

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Fan, L., Liu, Y., Ying, H. et al. Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultrasound Irradiation In Vitro. J Mol Neurosci 43, 541–548 (2011). https://doi.org/10.1007/s12031-010-9479-x

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  • DOI: https://doi.org/10.1007/s12031-010-9479-x

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