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Intracerebral Hemorrhage Induced Brain Injury Is Mediated by the Interleukin-12 Receptor in Rats

Authors Yue X, Liu L, Yan H, Gui Y, Zhao J, Zhang P

Received 26 August 2019

Accepted for publication 11 January 2020

Published 1 April 2020 Volume 2020:16 Pages 891—900

DOI https://doi.org/10.2147/NDT.S228773

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Jun Chen


Xuejing Yue,1 Lixia Liu,1 Haiqing Yan,2 Yongkun Gui,2 Jun Zhao,2 Ping Zhang2

1School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, People’s Republic of China

Correspondence: Ping Zhang
Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, People’s Republic of China
Tel +86-373-3029917
Email zhangpingsjnk@126.com

Background: IL-12 inhibition of the endothelial cell functions and angiogenesis is mediated by the cross-talk between the lymphocyte and the endothelial cells, which plays a key role in inhibiting the process of angiogenesis in the eyeballs and in malignant tumors.
Methods: We established the intracerebral hemorrhage (ICH) rat model, and IL-12 receptor beta monoclonal antibody was injected into the ICH rats. Western blot, immunofluorescence and RT-qPCR were used to detect the gene expression. Brain water content, EB staining, Garcia test, Beam walking test and wire hanging test were used to assess the injury of brain in ICH rats.
Results: IL-12 gene was significantly increase in hematoma border tissue of ICH rats, and IL-12 protein mainly localized in monocytes. Anti-IL-12 treatment with IL-12 monoclonal antibodies could not only significantly decrease the brain water content and EB content in brain tissues of ICH rats, but also significantly increase the score of the Garcia, Beam balance and the Wire hanging test in ICH rats. Moreover, anti-IL-12 treatment significantly decrease the expression of pro-inflammatory gene, inflammatory gene, p-JAK2/JAK2 and p-STAT4/STAT4 protein, but significantly increase the expression anti-inflammatory gene and CD31 protein, and M2 macrophage ratio in hematoma border tissues of ICH rats. In vitro, rmIL-12 inhibited the tube formation of brain microvascular endothelial cells (BMVES) in BMVES and bone marrow-derived monocytes (BMDM) co-culture systems, but not work in a separately cultured BMVES system. In addition, Fedratinib not only reduced p-JAK2/JAK2 and p-STAT4/STAT4 protein expression in BMDM after treating with b-FGF and rmIL-12, but also significantly increased the tube formation of BMVES in BMVES and BMDM co-culture systems after treating with b-FGF and rmIL-12.
Conclusion: Blockade of IL-12 receptor attenuated brain injury after ICH in rat by promoting angiogenesis, and the mechanism might be related to blocking IL-12 could inhibit M2 cell activation via the JAK2/STAT4 pathway.

Keywords: interleukin-12, intracerebral hemorrhage, vascular regeneration, macrophages
 

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