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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats

Authors: Qiquan Zhu, Budbazar Enkhjargal, Lei Huang, Tongyu Zhang, Chengmei Sun, Zhiyi Xie, Pei Wu, Jun Mo, Jiping Tang, Zongyi Xie, John H. Zhang

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Neuroinflammation and blood-brain barrier (BBB) disruption are two critical mechanisms of subarachnoid hemorrhage (SAH)-induced brain injury, which are closely related to patient prognosis. Recently, angiogenic factor with G-patch and FHA domain 1 (Aggf1) was shown to inhibit inflammatory effect and preserve vascular integrity in non-nervous system diseases. This study aimed to determine whether Aggf1 could attenuate neuroinflammation and preserve BBB integrity after experimental SAH, as well as the underlying mechanisms of its protective roles.

Methods

Two hundred forty-nine male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH. Recombinant human Aggf1 (rh-Aggf1) was administered intravenously via tail vein injection at 1 h after SAH induction. To investigate the underlying neuroprotection mechanism, Aggf1 small interfering RNA (Aggf1 siRNA) and PI3K-specific inhibitor LY294002 were administered through intracerebroventricular (i.c.v.) before SAH induction. SAH grade, neurological score, brain water content, BBB permeability, Western blot, and immunohistochemistry were performed.

Results

Expression of endogenous Aggf1 was markedly increased after SAH. Aggf1 was primarily expressed in endothelial cells and astrocytes, as well as microglia after SAH. Administration of rh-Aggf1 significantly reduced brain water content and BBB permeability, decreased the numbers of infiltrating neutrophils, and activated microglia in the ipsilateral cerebral cortex following SAH. Furthermore, rh-Aggf1 treatment improved both short- and long-term neurological functions after SAH. Meanwhile, exogenous rh-Aggf1 significantly increased the expression of PI3K, p-Akt, VE-cadherin, Occludin, and Claudin-5, as well as decreased the expression of p-NF-κB p65, albumin, myeloperoxidase (MPO), TNF-α, and IL-1β. Conversely, knockdown of endogenous Aggf1 aggravated BBB breakdown, inflammatory response and neurological impairments at 24 h after SAH. Additionally, the protective roles of rh-Aggf1 were abolished by LY294002.

Conclusions

Taken together, exogenous Aggf1 treatment attenuated neuroinflammation and BBB disruption, improved neurological deficits after SAH in rats, at least in part through the PI3K/Akt/NF-κB pathway.
Appendix
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Metadata
Title
Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats
Authors
Qiquan Zhu
Budbazar Enkhjargal
Lei Huang
Tongyu Zhang
Chengmei Sun
Zhiyi Xie
Pei Wu
Jun Mo
Jiping Tang
Zongyi Xie
John H. Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1211-8

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