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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Subarachnoid Hemorrhage | Research

The important role of connexin 43 in subarachnoid hemorrhage-induced cerebral vasospasm

Authors: Le Yang, Jian Yan, Jin-An Zhang, Xin-Hui Zhou, Chao Fang, Er-Ming Zeng, Bin Tang, Jian Duan, Guo-Hui Lu, Tao Hong

Published in: Journal of Translational Medicine | Issue 1/2019

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Abstract

Background

Gap junctions are involved in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the specific roles and regulatory functions of related connexin isoforms remain unknown. The aim of this study was to investigate the importance of connexin 43 (Cx43) in CVS and determine whether Cx43 alterations are modulated via the protein kinase C (PKC) signaling transduction pathway.

Methods

Oxyhemoglobin (OxyHb)-induced smooth muscle cells of basilar arterial and second-injection model in rat were used as CVS models in vitro and in vivo. In addition, dye transfer assays were used for gap junction-mediated intercellular communication (GJIC) observation in vitro and delayed cerebral ischemia (DCI) was observed in vivo by perfusion-weighted imaging (PWI) and intravital fluorescence microscopy.

Results

Increase in Cx43 mediated the development of SAH-induced CVS was found in both in vitro and in vivo CVS models. Enhanced GJIC was observed in vitro CVS model, this effect and increased Cx43 were reversed by preincubation with specific PKC inhibitors (chelerythrine or GF 109203X). DCI was observed in vivo on day 7 after SAH. However, DCI was attenuated by pretreatment with Cx43 siRNA or PKC inhibitors, and the increased Cx43 expression in vivo was also reversed by Cx43 siRNA or PKC inhibitors.

Conclusions

These data provide strong evidence that Cx43 plays an important role in CVS and indicate that changes in Cx43 expression may be mediated by the PKC pathway. The current findings suggest that Cx43 and the PKC pathway are novel targets for developing treatments for SAH-induced CVS.
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Metadata
Title
The important role of connexin 43 in subarachnoid hemorrhage-induced cerebral vasospasm
Authors
Le Yang
Jian Yan
Jin-An Zhang
Xin-Hui Zhou
Chao Fang
Er-Ming Zeng
Bin Tang
Jian Duan
Guo-Hui Lu
Tao Hong
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-02190-1

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