Dynamic Effects of Ioversol on the Permeability of the Blood-Brain Barrier and the Expression of ZO-1/Occludin in Rats
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Blood-brain barrier (BBB) dysfunction is involved in the pathogenesis of contrast-induced encephalopathy (CIE), which is a rare adverse event following angiography. In this study, we observed the dynamic effect and potential mechanism of ioversol on the BBB in rats. Eighty-one healthy rats were randomly divided into a normal control group (n = 9), ioversol group (n = 36), and 0.9% NaCl group (n = 36); the latter two groups were separately subdivided into four groups based on time points after treatment (0.5, 3, 6, and 24 h) (n = 9/group). Permeability of the BBB was measured by an Evans Blue (EB) assay. Levels of the tight junction (TJ) proteins ZO-1 and occludin were determined by western blot and immunofluorescence staining. EB content increased at 3 h after the administration of ioversol via the carotid artery and reached a peak at 6 h (P < 0.05), whereas it decreased to its normal level at 24 h. Western blot and immunofluorescence staining indicated that the expression of ZO-1 in brain tissues gradually decreased to its lowest level at 3 h, and then increased gradually, but was still lower than that of the normal control group at 24 h (P < 0.05). Occludin was similar, but its lowest expression appeared at 0.5 h. This study demonstrated that the permeability of BBB in rats increased first and then decreased after ioversol was injected into the carotid artery. The mechanism may be related to altered protein expression of TJs, which are important structures in BBB. Early intervention against TJ proteins may be an effective measure to prevent and treat CIE.
KeywordsContrast media Blood-brain barrier ZO-1 Occludin Dynamic
Common carotid artery
External carotid artery
Internal carotid artery
We thank the members of the Laboratory of Neurology, Xijing Hospital, Air Force Military Medical University. We also thank Prof. Ming Shi (Department of Neurology, Xijing Hospital, Air Force Military Medical University) for his advice on our experimental design, as well as Dr. Yajun Shi (Department of Neurology, Xijing Hospital, Air Force Military Medical University) for helping us with our experimental methods.
Author Contribution Statements
Heying Wang and Guilian Zhang wrote the main manuscript text. Heying Wang, Tao Li, Lili Zhao, Jiao Liu, and Guilian Zhang designed the experiment, Heying Wang, Man Sun, Yating Jian, Yiheng Zhang, Ye Li, and Meijuan Dang collected sample and analyzed the data. All authors reviewed the manuscript.
This work was supported by grants from the Shaanxi Science Research Project, China (No. 2010K16-08-02, 2015SF009) and the Second Affiliated Hospital Science Research Project, Xi’an Jiaotong University of China.
Compliance with Ethical Standards
All the study procedures complied with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80-23). The animal experiments were approved by the Committee on the Ethics of Animal Experiments of the Xi’an Jiaotong University College of Medicine.
Conflict of Interest
The authors declare that they have no conflict of interests.
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