Open Access

Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway

  • Authors:
    • Qiaosheng Wang
    • Yiyu Deng
    • Linqiang Huang
    • Wenxin Zeng
    • Shenglong Chen
    • Bo Lv
    • Wenqiang Jiang
    • Yongli Han
    • Hongguang Ding
    • Miaoyun Wen
    • Hongke Zeng
  • View Affiliations

  • Published online on: July 2, 2019     https://doi.org/10.3892/ijmm.2019.4262
  • Pages: 1078-1090
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the possible mechanisms by which hypertonic saline (HS) effectively ameliorates cerebral oedema via the vascular endothelial growth factor receptor 2 (VEGFR2)‑mediated endothelial nitric oxide synthase (eNOS) pathway of endothelial cells in rats. A middle cerebral artery occlusion (MCAO) model in Sprague‑Dawley rats and an oxygen‑glucose deprivation (OGD) model in cells were used in the present study. Evans blue (EB) staining and a horseradish peroxidase flux assay were performed to evaluate the protective effect of 10% HS on the blood‑brain barrier (BBB). The expression levels of vascular endothelial growth factor (VEGF), VEGFR2, zonula occludens 1 (ZO1) and occludin were quantified. The results demonstrated that 10% HS effectively reduced EB extravasation in the peri‑ischaemic brain tissue. At 24 h after MCAO, the protein expression levels of VEGF and VEGFR2 in the peri‑ischaemic brain tissue were downregulated following treatment with 10% HS. In vitro experiments demonstrated that the permeability of a monolayer endothelial cell barrier was decreased significantly following HS treatment. In addition, VEGF and VEGFR2 protein expression levels were increased in endothelial cells under hypoxic conditions, but that effect was suppressed by HS treatment. Furthermore, HS inhibited the downregulation of ZO1 and occludin effectively, possibly through the VEGFR2/phospholipase C γ1 (PLCγ1)/eNOS signalling pathway. In conclusion, 10% HS may alleviate cerebral oedema through reducing ischaemia‑induced BBB permeability, as a consequence of inhibiting VEGFR2/PLCγ1/eNOS‑mediated downregulation of ZO1 and occludin.

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September 2019
Volume 44 Issue 3

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Copy and paste a formatted citation
APA
Wang, Q., Deng, Y., Huang, L., Zeng, W., Chen, S., Lv, B. ... Zeng, H. (2019). Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway. International Journal of Molecular Medicine, 44, 1078-1090. https://doi.org/10.3892/ijmm.2019.4262
MLA
Wang, Q., Deng, Y., Huang, L., Zeng, W., Chen, S., Lv, B., Jiang, W., Han, Y., Ding, H., Wen, M., Zeng, H."Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway". International Journal of Molecular Medicine 44.3 (2019): 1078-1090.
Chicago
Wang, Q., Deng, Y., Huang, L., Zeng, W., Chen, S., Lv, B., Jiang, W., Han, Y., Ding, H., Wen, M., Zeng, H."Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway". International Journal of Molecular Medicine 44, no. 3 (2019): 1078-1090. https://doi.org/10.3892/ijmm.2019.4262